Dear reader of, please excuse the disruption. needs about $63500 in 2024. In 2023 we received donations of about $ 32200. Unfortunately, 99.8% of our readers do not donate. If everyone who reads this request makes a small contribution, our fundraising campaign for 2024 would be over after a few days. This donation request is displayed 23,000 times a week, but only 75 people donate. If you find useful, please take a minute and support with your donation. Thank you!

Since 01.06.2021 is supported by the non-profit ADxS e.V..

$8975 of $63500 - as of 2024-02-29
Header Image
Neurotransmitters during stress

Neurotransmitters during stress

Neurotransmitters are important factors in the development and mediation of stress within the body.

1. Neurotransmitters that activate the stress systems

The most important neurotransmitters that activate the stress systems of the CNS include1

  • from the locus coeruleus (A1/A2) and in the autonomic nervous system
    • Noradrenaline
  • from the hypothalamus
    • AVP
    • CRH
  • peptides derived from pro-opiomelanocortin
    • a-melanocyte stimulating hormone
    • ß-endorphin
  • from the raphe nuclei in the midbrain
    • Serotonin
  • from the posterior hypothalamic histaminergic system
    • Histamine

2. Disorders of the dopamine system during stress

Stress directly activates the dopaminergic system in the brain (CNS),2 which is centrally impaired in ADHD.

A meta-analysis of a large number of studies showed that dopamine levels and dopamine metabolism increase during acute stress, particularly in the PFC, but less so in subcortical areas.34

Acute stress increases DA levels in healthy rats

  • In the mPFC by 95 %
  • In the nucleus accumbens by 39 %
  • In the striatum by 25 %5

In stress responses, dopamine is mainly projected from the ventral tegmentum to the PFC and nucleus accumbens, with projection to the PFC being particularly stress-sensitive.674

  • Dopamine plays a role in the hedonic and reward aspects of stress.
  • The effects of stress on sexual activity and appetite as well as on the affinity for drug abuse are likely to be mediated by the dopamine system.
  • Dopamine increases the ability of neuronal information processing and thus the learning and information processing in relation to the stressor that has occurred.
  • The amygdala (the central nucleus) influences dopamine neurotransmission in the PFC. Lesions of the central amygdala block stress-induced dopamine release in the PFC. An infusion of AMPA into the central nucleus of the amygdala causes a rapid increase in dopamine in the PFC and (as a result) increased arousal.89 This is consistent with the role of the amygdala in coordinating neuronal systems to regulate behavior under stress.

Acute stress activates nigrostriatal dopamine neurons in two ways:10
- dopamine release through glutamatergic input to the dopamine cell bodies, which increases the firing rate of dopamine neurons
- dopamine synthesis is accelerated locally at the level of the dopamine terminal, which replaces the used dopamine
Thus, endogenous glutamate does not appear to influence dopamine release in the neostriatum, but glutamatergic projections influence dopamine synthesis via a direct cortico-striatal pathway.
Stress increases dopamine synthesis in the neostriatum. Striatal administration of NMDA or AMPA/kainate receptor antagonists attenuated this increase11, but administration into the substantia nigra did not.10

Stress inhibits all “uptake 2” transporters via the released corticosteroids (secured: by corticosterone). The uptake 2 transporters (PMAT, OCT 1 to OCT3) have a higher dopamine reuptake capacity than the uptake 1 transporters DAT and NET, with a lower affinity. Stress thus increases extracellular dopamine (and noradrenaline) through reduced uptake-2 transporter reuptake.
The uptake 2 transporters differ in their sensitivity to corticosterone depending on the species and tissue preparation.1213

  • OCT3 is more sensitive to corticosteroids than OCT1, OCT2 and PMAT
    • OCR3 shows IC50 values in the physiological range for corticosterone
  • OCT3 therefore acts as a critical mediator of stress and corticosteroid effects on neuronal and glial physiology and behavior

OCT3 mediates a strong modulatory influence of stress on the effects of noradrenaline, dopamine, serotonin and histamine via the stress-induced increase in glucocorticoid hormones in a rapid, non-genomic manner.14
The deactivation of OCT115 and OCT316 by corticosterone occurs

  • fast
  • through direct interaction of corticosterone with the transporter at specific sites

The main description of the PMAT can be found at Dopamine reuptake by the plasma membrane monoamine transporter (PMAT) in the article *Dopamine reuptake, dopamine degradation*and the main presentation of OCT follows on from there.

Chronic stress causes an increased increase in extracellular dopamine and noradrenaline in the PFC in response to a new acute stressor,1017 18 19 but not in the nucleus accumbens or neostriatum.

These findings are consistent with

  • our finding that ADHD symptoms resemble those of chronic severe stress
  • our assumption of dopaminergic hyperfunction in the PFC with simultaneous dopaminergic hypofunction in the striatum and nucleus accumbens in ADHD

2.1. Different types of stress cause different dopamine effects

Not all stress is the same. Depending on the type of stress, different effects are triggered on the dopamine system.

The types of stress differ according to:

  • Duration and intensity of stress
    Mild stress slightly increases the dopamine level (as well as the noradrenaline level) in the PFC and thus improves cognitive performance. Severe stress increases the dopamine level and the noradrenaline level in the PFC extremely and causes the PFC to shut down. Behavior control is outsourced to other parts of the brain.
  • Type of stressor Each stressor has its own specific effects on the neurotransmitters. Different stressors are, for example
    • Psychological stress
    • Physical pain
    • Injuries
    • Cold
    • Heat
    • Diseases

All stress symptoms have their own neurophysiological correlates.
A neurophysiological correlate means that a specific activity or change occurs in a certain area of the brain together with the symptom.

2.1.1. Mild/severe - short/long - early/late stress

  • Low stress levels are primarily processed in the mesoprefrontal system. Other ascending dopaminergic systems are not influenced by this.204 This could be due to a significantly lower number of inhibitory D2 autoreceptors in the mesoprefrontal area and extensive excitatory signals to the ventral tegmentum.
  • Mild stress increases dopamine, serotonin and noradrenaline metabolism21 in the mPFC22
    • Serotonin influences
      • The hypothalamus (part of the HPA axis / stress regulation axis)
      • The amygdala, which activates the HPA axis
      • The hippocampus, which inhibits the HPA axis.
  • Mild (not too prolonged) stress causes slightly increased noradrenaline and dopamine levels in the PFC.
  • Slightly elevated noradrenaline and dopamine levels increase the activity of the PFC and thus its cognitive and executive performance.
  • Highly elevated dopamine and/or noradrenaline levels switch off the PFC and shift behavioral control to other areas of the brain.
  • Short-term intense stress massively increases the dopamine level in the PFC
  • Low to moderate levels of stress increase extracellular23 dopamine levels in the nucleus accumbens2425 , but only in the NAc shell, not in the NAc nucleus2627 and PFC2425 , while high levels of stress (intense, chronic or unpredictable) decrease dopamine levels2829 . The increase in dopamine levels is greater in the PFC than in the striatum; within the striatal complex, it is greatest in the NAc shell.3023
  • Most stressors increase extracellular dopamine through an increase in dopamine efflux, an increase in neuronal activity in total firing rate and/or bursts:23
    • Food restriction/withdrawal
    • Bondage stress
    • Social defeats
    • Cold swimming
  • Chronic stressors (chronic cold exposure, chronic mild stress) have been shown to decrease population activity, i.e. the number of active neurons, but only in the medial and central VTA, not in the lateral VTA, and without decreasing the firing frequency. Bursts were slightly increased during chronic cold exposure.
    Stressors that increase dopamine firing also increase the risk of addiction and addiction relapses, which are prevented by blocking dopamine receptors.
  • Chronic early childhood stress reduces the dopamine level in the nucleus accumbens through downregulation.31
  • Dopamine in the mPFC normally suppresses mesolimbic dopamine transmission. However, this is no longer successful under extreme or unpredictable stress. Dopamine innervation also appears to be important for stress-induced activation of neurons in the stria terminalis (anterolateral BNST).324 which are involved in both the activation of higher-order stress-dependent circuits and the generation of coping behavior.
  • Increased dopamine levels in the mPFC lead to a reduction in dopamine levels in the nucleus accumbens in the striatum (reinforcement center), which could lead to the long-term overactivation of the dopamine transporters there by means of upregulation, which is a major problem in ADHD.
  • Chronic stress leads to a reduction in the dopamine level in the PFC via downregulation (increase in the number of dopamine transporters and dopamine receptors).
  • In chronic stress, the reduced dopamine level in the PFC after downregulation is nevertheless associated with
    • With overexcitation of the PFC
    • With a reduction in dopamine levels in the nucleus accumbens in the striatum
  • Chronic early childhood stress (daily hand-holding in rats, handling) leads to increased dopamine metabolism in the nucleus accumbens in adulthood. This results from a loss of inhibitory control by the right mPFC due to a dopamine deficiency found there. The dopamine deficiency in turn correlates with an increase in the number of dopamine transporters.33
  • The long-term nature (chronification) of stress and the degree of control over the stressor changes dopamine-dependent behaviors and the activation of afferents to the nucleus accumbens.344
  • While stress-induced dopamine release in the neostriatum is mediated by a glutamate effect on the dopamine cell body, stress-induced dopamine synthesis in the neostriatum is mediated by a glutamate effect on the dopamine nerve terminals10
  • Acute stress increases dopamine metabolism and dopamine release more in the PFC (+ 90 %) than in subcortical areas (nucleus accumbens + 40 %, neostriatum + 30 %)10
  • Previous chronic stress intensifies the reaction to an acute new stressor10
    • Only in mesocortical dopamine neurons
    • Not in the subcortical areas
  • Stress increases DOPAC in tissue35 and c-fos-expressing neurons36
    • In VTA
    • But not in substantia nigra

2.1.2. Different stressors

Each stressor has its own specific effect on dopamine.37 Psychological stress
  • Mental stress apparently only activates the dopaminergic D2 receptor system.38
  • Psychosocial stress
    • Increases the number of D2 receptor binding sites in the hippocampus.39
    • Reduces the binding of the ligand 3 H-WIN 35,428 for the dopamine transporter in the striatum after 4 weeks.38
    • Chronic psychosocial stress leads to a “shrinkage” of the dendrites of pyramidal neurons in the CA 3 region of the hippocampus.40
    • Chronic social stress reduced in mice41
      • In the hypothalamus: dopamine, noradrenaline and serotonin levels
      • In the PFC: serotonin and dopamine levels
    • Alcohol in the striatum did not increase dopamine levels in the defeated mice, while dopamine levels increased in non-defeated mice
  • Taking in the hand (of mice; handling)
    • Increases dopamine levels
      • In the mPFC4243
      • In the nucleus accumbens (albeit low)43
    • Does not change dopamine levels
      • In the striatum43
  • Acute physical constriction (fixation)
    • Increases dopamine in the mPFC and in the nucleus accumbens (mesolimbic dopamine system)44 and acetylcholine in the hippocampus.45
    • The dopamine increase in the mPFC and nucleus accumbens as well as the acetylcholine increase in the hippocampus also occur after the subsequent release, which is why this could be a correlate of emotional arousal due to a sudden change in environmental influences.4544
    • Increases the concentrations of the dopamine metabolite DOPAC in the PFC and nucleus accumbens46
    • Induces Fos immunoreactivity in dopamine neurons of the ventral tegmentum (VTA), but not in the substantia nigra47
  • Stress due to new environment
    • Increases dopamine levels in the right PFC48
  • Anxious behavior in the open environment
    • Correlates with increased dopamine levels in the right PFC49
  • Escape behavior in response to shocks
    • Correlates with increased dopamine levels in the right PFC50 Injuries and infections
  • Injuries and infections activate the D1 and D2 receptor system38 Repeated infliction of pain
  • Electric shocks
    • Activate the mesolimbic dopamine system4544
    • Increase FOS expression
      • In prelimbic and infralimbic cortexes51
      • In tyrosine hydroxylase-labeled neurons of the ventral tegmentum (VTA)51
  • Tail crushing in mice
    • Increase dopamine levels
      • In the mPFC43

      • In the nucleus accumbens (albeit low)43

      • Do not change dopamine levels

        • In the striatum43 Birth stress
  • Oxygen deprivation during birth leads to increased dopamine metabolism in the nucleus accumbens in adulthood. This results from a loss of inhibitory control by the right medial prefrontal cortex (PFC) due to a dopamine deficiency found there. The dopamine deficiency in turn correlates with an increase in the number of dopamine transporters.33 Hypotension
  • Increases the dopamine level in the mPFC524 Conditioned stress
  • Increases dopamine and serotonin levels in the brain
  • Does not change dopamine levels in
    • Perirhinal cortex534
    • Cingulate cortex534
    • Basolateral amygdala534
    • Striatum534
  • Acute conditioned stress should only increase the noradrenaline level in the mPFC, but not the dopamine level.54

2.2. Dopaminergic neurophysiological correlates of various stress reactions

Different stress reactions have different dopaminergic neurological correlates.

  • Jumpiness
    • Is controlled by increased dopamine in the dorsal striatum and by stimulation of the (dopamine-producing) substantia nigra pars compacta.2
    • Dopamine release in the mesolimbic system (nucleus accumbens = ventral striatum) through electrical stimulation of the ventral tegmentum promotes **aversively motivated learning
  • Learning from stressful experiences
    • Drug blockade of dopamine receptors in the amygdala prevents this.2
  • Maintaining attention to solve problems
    • Is controlled by the dorsolateral PFC.55
  • Selective attention (directing attention)
    • Is controlled by the dorsal anterior cingulate cortex.55
  • Hyperactivity
    • Is organized by the OFC56 and
    • The prefrontal motor cortex.55
  • Impulsiveness
    • Is organized by the OFC and the
    • Cortico-striatal-thalamocortical loop (cortex-striatum-thalamus control loop).57
  • Conditioned stress
    • Lesions of the left and right amygdala prevent an increase in dopamine in the mPFC and other stress responses to conditioned stress.22
  • Disorder of social behavior (Conduct Disorder, CD)
    • Controlled by a network of the ventromedial PFC and the limbic system58
  • Oppositional defiant behavior (ODD)
    • Controlled by a network of the ventromedial PFC and the limbic system58
  • Aggression
    • Controlled by a network of the ventromedial PFC and the limbic system58
  • Anxiety disorders
    • Controlled by a network of the ventromedial PFC and the limbic system58
  • Bipolar disorder
    • Controlled by a network of the ventromedial PFC and the limbic system58

3. Noradrenaline, adrenaline and stress

In the CNS, stress is primarily modulated by noradrenaline59

  • Moderate noradrenaline levels
    • Strengthen the function of the PFC
  • High noradrenaline levels
    • Switch off the PFC (which impairs analytical thinking)
    • Strengthen the sensorimotor and affective regions of the brain (which intensifies perception and emotion)

Acute stress has a primary noradrenergic effect on the postsynaptic response and reduces the phasic release of noradrenaline60

The activation of microglia by stress appears to be mediated by noradrenaline via β1- and β2-adrenoceptors, but not via β1-AR β3-adrenoceptors or α-adrenoceptors.61

Second graders showed increased cortisol levels on exam days and simultaneously decreased adrenaline and noradrenaline levels. The individual differences in secreted hormones were significantly related to personality variables observed in the classroom as well as the effects of academic stress:62

  • Social approach behavior correlated with higher cortisol and adrenaline levels
  • Fidgeting correlated with low adrenaline levels
  • Aggressiveness correlated with high noradrenaline levels
  • Inattention correlated with low noradrenaline levels

This section is based on the work of Belujon and Grace63

The locus coeruleus - noradrenaline system (LC-NE system)

  • is decisively involved in
    • Regulation of behavioral states
    • Regulation of stress reactions
      • Promotion of physiological stress reactions
    • Amplification of arousal states
      • Purpose: Adaptation to challenging situations
  • is activated by many stressors, e.g:
    • Bondage
    • Foot shocks
    • social stress
  • A stress load increases
    • the activity of locus coeruleus neurons
    • noradrenaline turnover in regions into which LC neurons project
      • in Amygdala
      • in Hippocampus
        • esp. vSub (primary output of the hippocampus)64
  • Lesions of the locus coeruleus
    • do not prevent hyperactivity of the HPA axis in response to chronic stress
    • attenuate the neuroendocrine hormonal reactions to acute stress
    • Activation of locus coeruleus neurons with CRF leads to the same behavior as acute stress

Locus coeruleus does not project itself directly into the HPA axis, but indirectly, via

  • Amygdala
    • in particular the basolateral nucleus (BLA)
      • here: increase in noradrenaline levels during stress
    • in addition, own BLA response to stress stimuli, which also activate locus coeruleus
    • projected onto HPA axis
  • Hippocampus
    • esp. vSub65
      • Key structure of the stress response
      • projected onto HPA axis
      • is involved in the processing of contextual information
        • processes the context of a stress load, which is important for effective adaptation
      • LC regulates inhibition or activation of vSub, which can support stress adaptation
      • vSub innervates limbic forebrain structures such as
        • PFC
        • Amygdala
        • PFC and amygdala project to paraventricular hypothalamus
        • as a result, vSub has an upstream influence on limbic stress integration
  • vSub and BLA inputs show reciprocal activation

Dysfunctional stress integration, as observed in psychiatric disorders, could be associated with dysregulation in the noradrenergic system, as stressors cause morphological changes in the hippocampus and BLA, e.g.

  • Hippocampus
    • dendritic atrophy (persistent / repeated stress)
  • BLA
    • Increase in dendrite and spine density (prolonged / repeated stress)
      • with strong correlation between synaptic plasticity and morphological changes of the spines
    • Increase in adrenergically regulated long-term potentiation (acute stress)

PFC, stress and noradrenaline:

  • mPFC another crucial component in stress response
    • is selectively activated by psychological and social stressors
    • modulates neuroendocrine function during stress via the LC-NE system
  • inevitable stress inhibits
    • Long-term potentiation in the BLA-PFC signal pathway
    • interferes with synaptic plasticity in the PFC-BLA signaling pathway
    • which indicates reciprocal interaction

4. Serotonin and stress

The ascending serotonergic pathways, which originate in the midbrain (nuclei raphe), accompany the central stress response derived from the locus ceruleus by releasing serotonin.1

There is a connection between serotonin and sensitivity to stress. However, the results are heterogeneous and the causes and correlations are still unclear.66
There is a connection between serotonin and cortisol levels.
Stress increases serotonin levels in healthy people67 as well as noradrenaline, dopamine and cortisol levels68.
Acute stress, on the other hand, is said to reduce serotonin production in the dorsal raphe nuclei, while fluoxetine stimulates serotonin production.69
Severe, life-threatening stress appears to increase the function and expression of serotonin 2-A receptors, as found in PTSD. Paradoxically, the PTSD medication 3,4-methylenedioxymethamphetamine acts as a serotonin 2-A receptor agonist.70

The adrenal cortex is removed so that cortisol can no longer be released,

  • This changes the release of serotonin in the dorsal raphe nuclei (DRN)
    • Not for nominal conditions
    • However, it decreased under stress
      Stimulation of the glucocorticoid receptors in the DRN then prevents the stress-induced serotonin blockade.66
  • Avoids unpredictable chronic stress71
    • The depression that normally occurs
    • But not the fear that normally arises
      • In the development of which the mineralocorticoid receptor is involved
      • Which is closely linked to cell proliferation in the hippocampus
  • This increases serotonin levels and TPH2 expression in the hippocampus in response to chronic unpredictable stress.71

Repeated stress increases serotonin production more than single stress72 and leads to apical dendrite reduction in the medial PFC, which reduces the number of excitatory postsynaptic events mediated by serotonin and orexin/hypocretin. Cortisol did not lead to this consequence. A GR antagonist given before stress avoided the reduction of serotonin-mediated excitatory postsynaptic events, but not those mediated by orexin/hypocretin.73

Chronic stress increases cortisol levels through the release of vasopressin rather than CRH.72

Cortisol increases the serotonin level in the amygdala and in the PFC74 as well as in the hippocampus.72 This is probably due to activation of the glucocorticoid receptors. This is because inhibition of monoamine oxidase increases the serotonin level, while a reduction in the cortisol level prevents this increase in serotonin (caused by monooxidase inhibition).75 This effect of cortisol lasts a long time (as with SSRIs) and presumably occurs through desensitization of the serotonin 1-A autoreceptor.76 However, the desensitization of the serotonin 1-A autoreceptor caused by SSRIs such as fluoxetine appears to act independently of the glucocorticoid receptor.77

Removal of the adrenal gland (in whose “cortexcortisol is produced) causes66

  • Unchanged serotonin transporter expression in the dorsal raphe nuclei (where serotonin is produced)
  • Unchanged [3H]cyano-imipramine binding to serotonin transporters in the dorsal raphe nuclei
  • Unchanged [3H]citalopram binding to serotonin transporters of the mesencephalon (midbrain)
  • Reduced serotonin reuptake in the mesencephalon (midbrain)
  • No change in serotonin transports in the dorsal raphe nuclei, medial raphe nuclei or in the mesencephalon with simultaneous long-term administration of MR- and GR-binding corticoids

In healthy rats, causes66

  • Acute corticosterone administration unchanged serotonin reuptake in the mesencephalon (midbrain)
  • A long-term infusion of dexamethasone (a stronger GR agonist than MR agonist)
    • Reduces serotonin transporter expression in the midbrain
    • But does not influence them in the hippocampus or PFC.
  • Short-term stress has no influence on serotonin transporter density in the midbrain
  • Prolonged stress (21 days)
    • Increases [3H]cyano-imipramine binding in the dorsal raphe nuclei
    • Increases (to a lesser extent) serotonin transporters in the medial raphe nuclei

Serotonin interacts extensively with BDNF in relation to78

  • Aggression
  • Depression
  • Drug addiction
  • Suicidal tendencies
  • Stress regulation
  • Brain plasticity

4.1. Serotonin deficiency and stress

Serotonin deficiency via deprivation of the serotonin precursor tryptophan activates the HPA axis in the same way as another stressor, but together with this it did not cause any synergistic stress axis effects.7980

SSRI administration reduced PTSD symptom severity in children and adults in one study.81

Serotonin deficiency is clinically evident in connection with78

  • Depression
  • Fear
  • Impulsiveness
  • Suicidal tendencies
  • Schizophrenia.

4.2. Serotonin transporters and stress

Reduced serotonin transporter binding affinity correlates with an increased cortisol stress response and increased anxiety.82

Various studies have been carried out on the serotonin transporter genotype

  • No significant influence on cortisol stress response or mood82
  • That the 5-HTTLPR short/short genotype correlates with a higher cortisol stress response
    • In young adults to psychosocial stress83
    • In newborns to a physical stressor84
  • That the group of 5-HTTLPR short genotypes (SS, SLG, LGLG, SLA, LGLA) correlated with a greater frequency of early childhood stress experiences in the first 5 years of life compared to 5-HTTLPR long/long (LALA) in younger adults, but not in children.85
  • Twins who had suffered bullying had a higher serotonin transporter methylation at the age of 10 than their twin siblings without bullying experience. Twins with later (!) bullying experience already showed an increase in methylation at the age of 5, i.e. before this (!) bullying experience, compared to their non-bullied twin siblings. Children with higher serotonin transporter methylation levels showed a flattened cortisol stress response.86 This could be related to the fact that people with impairments (such as ADHD) are more likely to be victims of violence. ADHD increased the probability 2.7-fold according to one study.87
  • That the group of 5-HTTLPR short genotypes (SS, SLG, LGLG, SLA, LGLA) in combination with many early childhood stress experiences in the first 5 years of life
    • Correlates with a high cortisol stress response to the TSST.85 Similar results were found in several other studies.888990
  • That 5-HTTLPR long/long (LALA) in combination with few early childhood stress experiences in the first 5 years of life
    • Correlates with a high cortisol stress response to the TSST88
    • Which another study only found in younger adults85
    • While another study found no correlation90

5. Histamine and stress

The posterior hypothalamic histaminergic system accompanies the central stress response derived from the locus coeruleus by releasing histamine.1

6. The stress hormones CRH, cortisol and stress

CRH and cortisol are not neurotransmitters, but hormones that are produced by the hypothalamus as the first stage of the HPA axis (CRH) and the adrenal cortex as the last stage of the HPA axis (cortisol).
As the HPA axis is essential for understanding stress and ADHD, we refer here to the detailed description at The HPA axis / stress regulation axis and ⇒ Cortisol in ADHD.

Older adults

  • With a low number of stressful life experiences in the first 15 years of life showed the highest cortisol stress response85
  • With a high number of stressful life experiences in the first 15 years of life showed the lowest cortisol stress response85

While some authors85 regard a low cortisol stress response as a measure of a healthy reaction, we ask ourselves whether a medium cortisol stress response is not healthy and whether a particularly low cortisol stress response, as well as an excessive cortisol stress response, is a sign of a stress system imbalance, as is also the case with the cortisol stress response.

7. Stress/ADHD symptoms due to too high or too low catecholamine levels

7.1. Optimal neurotransmitter levels = optimal information transmission

Optimal transmission of information between brain synapses requires an optimal level of the respective neurotransmitters. A neurotransmitter level that is too low leads to an almost identical signal transmission disorder as a neurotransmitter level that is too high (reversed-U theory).91929394939596979899100101102

For optimal signaling, the pyramidal cells of the PFC require moderate stimulation of D1 receptors by dopamine and α2A receptors by norepinephrine. Dopamine binding to D1 receptors reduces the noise of the input signal in the PFC by reducing signals from unneeded external sources, while noradrenaline amplifies the incoming signal from external sources via α2A receptors.103

Increased DA and NE levels cause additional occupancy of receptors, which reduces attention. Reduced DA and NE levels result in all incoming signals being identical, which reduces concentration on individual tasks.

A DA and/or NE level that is too high or too low therefore leads to very similar symptoms due to suboptimal signal transmission in the PFC.104

Therefore, a medication that increases neurotransmitter levels and works well at low doses can, at higher doses, cause the very symptoms that it avoids at low doses. It is therefore a mistake to start medication for ADHD at the desired target dose or to dose it quickly. It is better to start the titration phase (medication phase) particularly slowly and low than too quickly and too high.


Adult non-smokers were treated with nicotine patches in a small study.
Those with poor concentration improved, while those with good concentration worsened.105
Nicotine has a similar effect to stimulants, only cholinergic instead of dopaminergic; it therefore increases the level of the neurotransmitter acetylcholine. Too low an acetylcholine level causes concentration problems.
Nicotine patches are potentially effective medication for ADHD.
Nicotine for ADHD

7.2. Stress/ADHD symptoms due to increased catecholamine levels (DA / NE)

7.2.1. Acute stress increases dopamine levels in the mPFC, striatum and nucleus accumbens

Stress increases dopamine levels in healthy rats

  • In the mPFC by 95 %
  • In the nucleus accumbens by 39 %
  • In the striatum by 25 %106107

Stress involves a phasic (i.e. short-term) increase in dopamine levels.108

7.2.2. Mild acute stress = slight increase in NE/DA = increased cognitive performance

The mild stress reactions of the autonomic nervous system are mediated by acetylcholine and adrenaline.

In the central nervous system (brain), slight increases in dopamine and/or noradrenaline levels cause increased performance of the PFC (except in carriers of the COMT Met158Met gene polymorphism).109110111112113

If this does not solve the problem (the stressor is not eliminated), dopamine and noradrenaline levels continue to rise. High noradrenaline levels activate the HPA axis (stress axis), which only comes into action when stress is difficult to cope with.

7.2.3. Severe acute stress = strong increase in NE/DA and cortisol = reduced cognitive performance High noradrenaline level blocks PFC

In contrast to mild increases in noradrenaline, which stimulate the PFC, strong increases in noradrenaline switch off the PFC and shift behavioral control to posterior brain regions.59114115116117118119

This should correspond to the effect described by Dietrich120 with reference to Mobbs et al121 as posteriorization. High cortisol levels block PFC

High cortisol levels, which occur in particular in ADHD-I and SCT during acute stress, additionally stimulate the noradrenaline α1 receptors in the PFC, via which noradrenaline already impairs the function of the PFC and working memory. The simultaneous addressing of these receptors by noradrenaline and cortisol intensifies this effect.122
In addition, the shift of control from cognitive brain regions (PFC and hippocampus) to more behavioral brain regions (such as aymgdala and dorsal striatum) is regulated by the cortisolergic mineralocorticoid receptors (MR) and glucocorticoid receptors (GR).123

Cortisol, which is often elevated as a stress response in ADHD-I and presumably also SCT, blocks the retrieval of declarative (explicit) memory via the glucocorticoid receptors (GR) in the PFC and hippocampus. The non-declarative (implicit, intuitive) memory is not affected.124 This could explain the thinking and memory blocks often associated with ADHD-I and also why ADHD-I sufferers are often said to have a higher level of intuition. In any case, it would stand to reason that the shift in the focus of memory skills leads to a shift in problem-solving patterns. Trappmann-Korr calls this “holistic” perception. However, our own data collection has so far shown that a self-assessment of being intuitive is present in 69% of ADHD-HI sufferers and only 60% of ADHD-I sufferers. (n = 1,100, as of August 2019)
It is likely that not only the retrieval (remembering), but also the acquisition (learning) and memory consolidation (long-term storage) of information is impaired. Consolidation occurs particularly during sleep in the first half of the night, which is characterized by particularly low basal cortisol levels. Consolidation can be prevented by low cortisol levels.124

Cortisol stress response does not correlate with mental blocks

Our hypothesis that thinking blocks would occur less frequently in ADHD-HI than in ADHD-I was not confirmed by the analysis of around 1700 data sets from the ADxS online symptom test. According to our data, thinking blocks occurred with approximately the same frequency in ADHD-HI as in ADHD-I.

There is evidence that high noradrenaline levels switch off the PFC via α1 receptors.

We had assumed that ADHD-HI sufferers (due to a reduced noradrenaline stress response in parallel to the reduced cortisol stress response) would suffer less frequent blockages of the PFC and the associated thinking and decision-making problems, while ADHD-I sufferers (without hyperactivity/impulsivity), due to an increased phasic cortisol stress response and an associated increased phasic noradrenaline release to acute stress, would suffer a frequent short-term exaggerated stress response and a more frequent shutdown of the PFC (by noradrenaline and cortisol), which could trigger more frequent thinking blocks. Neurotransmitters during stress

Since the intensity of norepinephrine release stimulates the intensity of cortisol release, we hypothesized that cortisol and norepinephrine stress responses would run in parallel. Since several data suggest that ADHD-I correlates with increased cortisol stress responses, if cortisol and norepinephrine stress responses were correlated, it would have been logical that the increased cortisol stress responses typical of ADHD-I would be associated with increased stress-induced release of norepinephrine and resulting increased α1-adrenergic receptor activation.

However, the equal frequency of thought blocks in ADHD-HI and ADHD-I sufferers suggests that this hypothesis is not correct. Details

Since the PFC controls the HPA axis, it is additionally disinhibited by the loss of control by the PFC.
Other voices distinguish between short-term stress, which increases the cognitive performance of the PFC, and long-term stress, which reduces it,125 which should be the same result.

Slightly elevated catecholamine levels activate postsynaptic alpha2A adrenoceptors (by noradrenaline) and D1 receptors (by dopamine) and thus improve the prefrontal regulation of behavior and attention, while strongly elevated catecholamine levels worsen prefrontal functions by stimulating noradrenergic alpha1 adrenoceptors and (excessively) dopaminergic D1 receptors.12698
Alpha1 adrenoceptors are less sensitive than alpha2A adrenoceptors and therefore only respond to higher noradrenaline levels. If the noradrenaline level is so high that it can activate not only the alpha2a but also the alpha1 adrenoceptors, the alpha1 adrenoceptors inhibit the cognitive performance of the PFC.127116128129
See also the description of adrenoceptors = noradrenaline receptors at Noradrenaline.

Physiological stressors such as traumatic brain injury130 or hypoxia131 appear to trigger similar physiological effects in the PFC as psychological stress. The physical stressors also induce the release of catecholamines in the mPFC and activate the same intracellular signaling events (e.g. activation of the cAMP-PKA pathway) that are associated with loss of dendritic spines and impairment of working memory. Apparently, various stressors (physical as well as psychological) can impair the structure and function of the PFC.126

Alpha1-adrenoceptor antagonists (blockers) are used to treat PTSD.

Increases in cortisol are associated with stress-induced release of noradrenaline and α1-adrenergic receptor activation.132133
The increase in cortisol levels following stress is mediated by activation of the adrenergic system and the α1-adrenergic receptors, in that a strong increase in noradrenaline levels activates alpha1-adrenoceptors in the hypothalamus and thus leads to the release of the stress hormone CRH, which activates the further stages of the HPA axis (release of ACTH and cortisol).132134133135
CRH reduces the performance of the PFC (especially working memory) in a dose-dependent manner. CRH antagonists neutralize this effect.136137

The activation of alpha1-adrenoceptors by high noradrenaline levels thus causes high cortisol levels and attention problems.138

The noradrenaline level in the OFC and in the amygdala correlates with the activation of the HPA axis in healthy people. In severely overweight people, however, this correlation is inverted.135

7.2.4. PFC and amygdala - stress phenotypes

The activity of the PFC is inverse to the activity of the amygdala. An active PFC correlates with a less active amygdala and vice versa.139
It is known that anxiety and depression occur more frequently in people who internalize stress, i.e. eat stress into themselves (internalizing, ADHD-I subtype) rather than acting it out (externalizing, ADHD-HI/ADHD-C). In the latter, externalizing disorders such as aggression disorders (oppositional defiant disorder; social behaviour disorder, borderline) predominate.

With this in mind, the fact that ADHD-I has a higher incidence of disorders associated with an activated amygdala, such as anxiety and depression, suggests that the PFC is more frequently deactivated in ADHD-I than in ADHD-HI. Together with the fact that elevations in cortisol are associated with stress-induced release of norepinephrine and α1-adrenergic receptor activation,132133 this leads us to hypothesize that in ADHD-I, norepinephrine release in response to acute stress is likely to be very frequently excessive, analogous to cortisol release, which causes a more frequent shutdown of the PFC and a shift of behavioral control to subcortical brain regions, while in ADHD-HI, which is often associated with a reduced release of cortisol in response to acute stress, there should be a correlating reduced release of noradrenaline, which less frequently (and perhaps even too rarely in view of the inability to recover) leads to a downregulation of the PFC.

7.2.5. Dopamine for stress and ADHD

DAT knockout mice, which have almost no dopamine transporters (DAT) (i.e. represent a kind of neurological anti-model of ADHD in which too many DAT are present), have some of the same symptoms as ADHD sufferers:140

  • Hyperactive
  • Learning problems
  • Memory problems

The disorders that often occur comorbidly with ADHD

  • Conduct disorder (CD)
  • Oppositional defiant behavior (ODD)
  • Psychosis
  • Bipolar

are typically associated with extremely elevated dopamine levels in some areas of the brain.104

7.3. Stress/ADHD symptoms due to low catecholamine levels (DA / NE)

Massive dopamine deficiency in the striatum leads to a massive disruption of drive. The interest In pleasure is reduced, while the pleasureability itself is not impaired.

However, dopamine deficiency is only one way of causing the symptoms mentioned. Excess dopamine causes largely identical symptoms, as the main factor is a deviation from an optimal dopamine level for signal transmission (see 1.1. and 1.2. above).

  • Rats whose ascending dopaminergic pathways were almost completely destroyed, resulting in 99% less dopamine being available, subsequently lacked the drive to consume their previously preferred sugar solution. This phenomenon was therefore caused by a lack of dopamine in the reinforcement center of the brain (striatum). The animals’ ability to perceive pleasure when they were given the sugar solution remained unchanged, as evidenced by the typical tongue movements that rats make in response to foods they find pleasant. This pleasure response could also be enhanced by hedonically activating substances (e.g. benzodiazepines) and weakened by simultaneous unpleasant stimuli.141142
  • The neurotoxin 6-hydroxydopamine selectively destroys dopaminergic neurons. Animals treated in this way develop hyperactive behavior143
    • According to other accounts, 6-hydroxydopamine has a more noradrenergic effect.144 Noradrenaline is also significantly involved in ADHD.
    • Dopamine level disturbances caused by 6-hydroxydopamine showed a great importance of the D4 receptors in the caudate nucleus (but not of D2 receptors) in the development of hyperactivity.145
  • Those affected by the encephalitis epidemic of 1914 to 1917 developed typical ADHD symptoms. Children developed hyperactive motor skills, adults Parkinson’s symptoms. Encephalitis destroys the cells in the substantia nigra that produce dopamine. This cause could be reproduced in animal experiments as the trigger for the symptoms. The symptoms are therefore the result of dopamine deficiency.146 When diagnosing ADHD, encephalitis must still be clarified as a differential diagnosis.
  • Perinatal hypoxia, which leads to early childhood brain damage (FKHS), causes the destruction of dopaminergic cells in the striatum, which reduces the dopamine level in the striatum by up to 70 %.
  • In Parkinson’s sufferers, the cells of the substantia nigra are damaged, which reduces the synthesis of dopamine by up to 90 percent. This causes motor impairments such as rigor, tremor and akinesia. Depression is many times more common in Parkinson’s sufferers, which is also likely to be due to the dopamine deficiency.147
  • Cocaine or amphetamine abuse causes a downregulation of the body’s own dopamine synthesis. After stopping the cocaine intake, hyperactivity occurs as a withdrawal symptom due to the now too low dopamine level.148
  • Nicotine, which is consumed earlier and more frequently by ADHD sufferers,149 increases the release of dopamine in nigrostriatal and mesolimbic areas and thus improves attention.150151
  • Toxins such as polychlorinated biphenyls, which inhibit the synthesis of dopamine and the storage of dopamine in the vesicles and its release, thereby causing dopamine levels to be too low, also cause hyperactivity and impulsivity (in rats even at sub-toxic doses).152
  • Dysphoria is caused by a lack of dopamine (according to Wender-Utah, dysphoria during inactivity is a core symptom of ADHD in adults).153

The fact that dopamine deficiency is involved in the mediation of ADHD symptoms is shown by the very good effect of drugs that increase dopamine levels or mediate an improved response to dopamine. Stimulants (methylphenidate, amphetamine drugs) and atomoxetine act as dopamine reuptake inhibitors (which increase the availability of dopamine in the synaptic cleft) and stimulate dopamine production.

However, not all medications that increase dopamine levels are helpful for ADHD. The dopamine agonists L-dopa (levodopa), amantadine and piribidel, for example, have no positive effects on ADHD despite their dopamine-increasing effect.154

  • Levodopa is a precursor of dopamine (prodrug) that can cross the blood-brain barrier and is metabolized to dopamine in the brain.155 Levodopa is helpful for Parkinson’s disease and restless legs syndrome, both of which are characterized by a lack of dopamine, but is not effective for ADHD.
  • Amantadine is a weak glutamate receptor antagonist of the NMDA receptor, increases the release of dopamine and acts as a dopamine reuptake inhibitor. Its effect in Parkinson’s disease is controversial. In some cases, a weak activating effect on arousal is reported.156
  • Piribedil is a piperazine derivative and therefore a non-ergot dopamine agonist.
    Piribedil is an agonist of the D2 and D3 dopamine receptors and an antagonist of the α2 adrenoreceptor subtypes α2A and α2C. It is used to treat Parkinson’s disease, also in combination with levodopa.

While short-term stress without ADHD leads to an excess of catecholamines (dopamine and noradrenaline) in the PFC,140 early long-term stress leads to a downregulation of the dopamine and noradrenaline systems. For example, chronic early childhood stress reduces dopamine levels in the nucleus accumbens.31

Exercise-induced stress in rats causes a later downregulation of dopamine in the ventral tegmentum via noradrenaline at beta-adrenoceptors of the amygdala.157

Whether there is too little or too much (tonic = long-term) catecholamine in ADHD is the subject of intense debate.158
The disagreement among scientists indicates that both variants occur. It is possible that the subtypes and individual symptom combinations of those affected differ. It is undisputed that many ADHD sufferers have reduced dopamine levels in the PFC and striatum.
According to current knowledge, we assume that ADHD is caused by a deficiency of dopamine and noradrenaline in the dlPFC, striatum and probably also the cerebellum.

The typical ADHD medications (stimulants and atomoxetine act as dopamine and noradrenaline reuptake inhibitors. Stimulants increase the DA and NE levels in the PFC and striatum, atomoxetine only in the PFC) increase the availability of these neurotransmitters in the synaptic cleft.

Conversely, this should mean that stimulants do not work in the case of stress-induced “sham ADHD” symptoms, as they further increase the dopamine level, which is already above the optimum, and thus even further away from the functional level. While dopamine and noradrenaline levels (or the DA / NE effect) are reduced in ADHD, people (with acute but not chronic long-term stress) without ADHD do not have reduced but rather increased levels of dopamine and noradrenaline. Therefore, a further increase in DA and NA levels in non-affected people should tend to worsen the symptoms, whereas they are helpful in ADHD.

Some studies suggest that these considerations may be justified:

Only low doses of methylphenidate cause an improvement in attention and executive abilities even in non-stressed healthy individuals, while higher doses have a negative effect.98 This corresponds to the slight increase in DA and NE during mild stress, which increases cognitive abilities, and the strong increase in DA and NE during severe stress, which switches off the PFC.

However, many ADHD sufferers only respond to some ADHD medications, meaning that in practice no diagnostic conclusions can be drawn from the non-effect of medication alone. This is due to the major differences described above in terms of which stress has caused downregulation in which areas of the brain in each affected person.

  1. Chrousos (2009): Stress and disorders of the stress system. Nat Rev Endocrinol. 2009 Jul;5(7):374-81. doi: 10.1038/nrendo.2009.106. PMID: 19488073. REVIEW

  2. Rensing, Koch, Rippe, Rippe (2006): Der Mensch im Stress; Psyche, Körper, Moleküle; Elsevier Spektrum (heute: Springer), Kapitel 4: neurobiologische Grundlagen von Stressreaktionen, Seite 90

  3. Finlay, Zigmond (1997): The effects of stress on central dopaminergic neurons: possible clinical implications. Neurochem Res. 1997 Nov;22(11):1387-94. REVIEW

  4. Steckler, Kalin, Reul (2005): Handbook of Stress and the Brain, Teil 1; Elsevier, Seite 624 f

  5. Abercrombie, Keefe, DiFrischia, Zigmond (1989): Differential Effect of Stress on In Vivo Dopamine Release in Striatum, Nucleus Accumbens, and Medial Frontal Cortex. Journal of Neurochemistry, 52: 1655–1658; doi:10.1111/j.1471

  6. Roth, Tam, Ida, Yang, Deutch (1988), Stress and the Mesocorticolimbic Dopamine Systemsa. Annals of the New York Academy of Sciences, 537: 138–147. doi:10.1111/j.1749-6632.1988.tb42102.x

  7. Pani, Porcella, Gessa (2000): The role of stress in the pathophysiology of the dopaminergic system; Molecular Psychiatry 5, 14–21 (2000); doi:10.1038/

  8. Stalnaker, Berridge (2003): AMPA receptor stimulation within the central nucleus of the amygdala elicits a differential activation of central dopaminergic systems. Neuropsychopharmacology. 2003 Nov;28(11):1923-34

  9. Steckler, Kalin, Reul (2005): Handbook of Stress and the Brain, Teil 1; S. 624 f

  10. Finlay JM, Zigmond MJ (1997): The effects of stress on central dopaminergic neurons: possible clinical implications. Neurochem Res. 1997 Nov;22(11):1387-94. doi: 10.1023/a:1022075324164. PMID: 9355111. REVIEW

  11. Castro SL, Sved AF, Zigmond MJ (1996): Increased neostriatal tyrosine hydroxylation during stress: role of extracellular dopamine and excitatory amino acids. J Neurochem. 1996 Feb;66(2):824-33. doi: 10.1046/j.1471-4159.1996.66020824.x. PMID: 8592158.

  12. Koepsell H, Lips K, Volk C (2007): Polyspecific organic cation transporters: structure, function, physiological roles, and biopharmaceutical implications. Pharm Res. 2007 Jul;24(7):1227-51. doi: 10.1007/s11095-007-9254-z. PMID: 17473959. REVIEW

  13. Hill JE, Makky K, Shrestha L, Hillard CJ, Gasser PJ (2011): Natural and synthetic corticosteroids inhibit uptake 2-mediated transport in CNS neurons. Physiol Behav. 2011 Aug 3;104(2):306-11. doi: 10.1016/j.physbeh.2010.11.012. PMID: 21081135.

  14. Gasser PJ, Lowry CA (2018): Organic cation transporter 3: A cellular mechanism underlying rapid, non-genomic glucocorticoid regulation of monoaminergic neurotransmission, physiology, and behavior. Horm Behav. 2018 Aug;104:173-182. doi: 10.1016/j.yhbeh.2018.05.003. PMID: 29738736; PMCID: PMC7137088. REVIEW

  15. Volk C, Gorboulev V, Kotzsch A, Müller TD, Koepsell H (2009): Five amino acids in the innermost cavity of the substrate binding cleft of organic cation transporter 1 interact with extracellular and intracellular corticosterone. Mol Pharmacol. 2009 Aug;76(2):275-89. doi: 10.1124/mol.109.054783. PMID: 19435783.

  16. Gasser PJ (2019): Roles for the uptake2 transporter OCT3 in regulation of dopaminergic neurotransmission and behavior. Neurochem Int. 2019 Feb;123:46-49. doi: 10.1016/j.neuint.2018.07.008. PMID: 30055194; PMCID: PMC6338509. REVIEW

  17. Gresch PJ, Sved AF, Zigmond MJ, Finlay JM (1995): Local influence of endogenous norepinephrine on extracellular dopamine in rat medial prefrontal cortex. J Neurochem. 1995 Jul;65(1):111-6. doi: 10.1046/j.1471-4159.1995.65010111.x. PMID: 7790854.

  18. Blanc G, Hervé D, Simon H, Lisoprawski A, Glowinski J, Tassin JP (1980): Response to stress of mesocortico-frontal dopaminergic neurones in rats after long-term isolation. Nature. 1980 Mar 20;284(5753):265-7. doi: 10.1038/284265a0. PMID: 7189015.

  19. Kalivas PW, Duffy P (1989): Similar effects of daily cocaine and stress on mesocorticolimbic dopamine neurotransmission in the rat. Biol Psychiatry. 1989 Apr 1;25(7):913-28. doi: 10.1016/0006-3223(89)90271-0. PMID: 2541803.

  20. Horger, Roth (1996): The Role of Mesoprefrontal Dopamine Neurons in Stress; Critical Reviews in Neurobiology DOI: 10.1615/CritRevNeurobiol.v10.i3-4.60, pages 395-418

  21. Bliss, Ailion, Zwanziger (1968): Metabolism of norepinephrine, serotonin and dopamine in rat brain with stress. J Pharmacol Exp Ther 164:122–134.

  22. Goldstein, Rasmusson, Bunney, Roth (1996): Role of the Amygdala in the Coordination of Behavioral, Neuroendocrine, and Prefrontal Cortical Monoamine Responses to Psychological Stress in the Rat; Journal of Neuroscience 1 August 1996, 16 (15) 4787-4798

  23. Marinelli M, McCutcheon JE (2014): Heterogeneity of dopamine neuron activity across traits and states. Neuroscience. 2014 Dec 12;282:176-97. doi: 10.1016/j.neuroscience.2014.07.034. PMID: 25084048; PMCID: PMC4312268. REVIEW

  24. Imperato A, Puglisi-Allegra S, Casolini P, Zocchi A, Angelucci L. Stress-induced enhancement of dopamine and acetylcholine release in limbic structures: role of corticosterone. Eur J Pharmacol. 1989 Jun 20;165(2-3):337-8. doi: 10.1016/0014-2999(89)90735-8. PMID: 2776836.

  25. Tidey JW, Miczek KA (1996): Social defeat stress selectively alters mesocorticolimbic dopamine release: an in vivo microdialysis study. Brain Res. 1996 May 20;721(1-2):140-9. doi: 10.1016/0006-8993(96)00159-x. PMID: 8793094.

  26. Kalivas PW, Duffy P (1995): Selective activation of dopamine transmission in the shell of the nucleus accumbens by stress. Brain Res. 1995 Mar 27;675(1-2):325-8. doi: 10.1016/0006-8993(95)00013-g. PMID: 7796146.

  27. Barrot M, Marinelli M, Abrous DN, Rougé-Pont F, Le Moal M, Piazza PV (2000): The dopaminergic hyper-responsiveness of the shell of the nucleus accumbens is hormone-dependent. Eur J Neurosci. 2000 Mar;12(3):973-9. doi: 10.1046/j.1460-9568.2000.00996.x. PMID: 10762327.

  28. Di Chiara G, Loddo P, Tanda G (1999): Reciprocal changes in prefrontal and limbic dopamine responsiveness to aversive and rewarding stimuli after chronic mild stress: implications for the psychobiology of depression. Biol Psychiatry. 1999 Dec 15;46(12):1624-33. doi: 10.1016/s0006-3223(99)00236-x. PMID: 10624543.

  29. Mangiavacchi S, Masi F, Scheggi S, Leggio B, De Montis MG, Gambarana C (2001): Long-term behavioral and neurochemical effects of chronic stress exposure in rats. J Neurochem. 2001 Dec;79(6):1113-21. doi: 10.1046/j.1471-4159.2001.00665.x. PMID: 11752052.

  30. Marinelli M (2007): Dopaminergic reward pathways and the effects of stress. In: Al’Absi M, editor. Stress and Addiction: Biological and Psychological Mechanisms. Academic Press; Burlington: 2007. pp. 41–84

  31. Karkhanis, Rose, Weiner, Jones (2016): Early-Life Social Isolation Stress Increases Kappa Opioid Receptor Responsiveness and Downregulates the Dopamine System. Neuropsychopharmacology. 2016 Aug;41(9):2263-74. doi: 10.1038/npp.2016.21.

  32. Kozicz, T. (2002), Met-enkephalin immunoreactive neurons recruited by acute stress are innervated by axon terminals immunopositive for tyrosine hydroxylase and dopamine-α-hydroxylase in the anterolateral division of bed nuclei of the stria terminalis in the rat. European Journal of Neuroscience, 16: 823–835. doi:10.1046/j.1460-9568.2002.02129.x

  33. Brake, Sullivan, Gratton (2000): Perinatal Distress Leads to Lateralized Medial Prefrontal Cortical Dopamine Hypofunction in Adult Rats; Journal of Neuroscience 15 July 2000, 20 (14) 5538-5543

  34. Cabib, Puglisi-Allegra (1996): Stress, depression and the mesolimbic dopamine system; Psychopharmacology; December 1996, Volume 128, Issue 4, pp 331–342

  35. Deutch AY, Tam SY, Roth RH (1985): Footshock and conditioned stress increase 3,4-dihydroxyphenylacetic acid (DOPAC) in the ventral tegmental area but not substantia nigra. Brain Res. 1985 Apr 29;333(1):143-6. doi: 10.1016/0006-8993(85)90134-9. PMID: 3995282.

  36. Deutch AY, Lee MC, Gillham MH, Cameron DA, Goldstein M, Iadarola MJ (1991): Stress selectively increases fos protein in dopamine neurons innervating the prefrontal cortex. Cereb Cortex. 1991 Jul-Aug;1(4):273-92. doi: 10.1093/cercor/1.4.273. PMID: 1668366.

  37. Spencer, Ebner, Day (2004): Differential involvement of rat medial prefrontal cortex dopamine receptors in modulation of hypothalamic- pituitary-adrenal axis responses to different stressors, European journal of neuroscience, vol. 20, no. 4, pp. 1008-1016, doi: 10.1111/j.1460-9568.2004.03569.x.

  38. Isovich, Mijnster, Flügge, Fuchs (2000): Chronic psychosocial stress reduces the density of dopamine transporters. Eur J Neurosci. 2000 Mar;12(3):1071-8.

  39. Flügge, van Kampen, Mijnster (2004): Perturbations in brain monoamine systems during stress. Cell Tissue Res. 315:1-14.

  40. Fuchs, Flügge (2004): Psychosozialer Stress verändert das Gehirn, Neuroforum 2/04, 195

  41. Favoretto, Nunes, Macedo, Lopes, Quadros (2020): Chronic social defeat stress: Impacts on ethanol-induced stimulation, corticosterone response, and brain monoamine levels. J Psychopharmacol. 2020 Jan 22:269881119900983. doi: 10.1177/0269881119900983. PMID: 31965898.

  42. Kawahara, Kawahara, Westerink (1999): Comparison of effects of hypotension and handling stress on the release of noradrenaline and dopamine in the locus coeruleus and medial prefrontal cortex of the rat; Naunyn-Schmiedeberg’s Archives of Pharmacology; July 1999, Volume 360, Issue 1, pp 42–49

  43. Cenci, M. A., Campbell, K., Wictorin, K. and Björklund, A. (1992), Striatal c-fos Induction by Cocaine or Apomorphine Occurs Preferentially in Output Neurons Projecting to the Substantia Nigra in the Rat. European Journal of Neuroscience, 4: 376–380. doi:10.1111/j.1460-9568.1992.tb00885.x, zitiert nach Steckler, Kalin, Reul (2005): Handbook of Stress and the Brain, Teil 1; Elsevier, Seite 624 f

  44. Steckler, Kalin, Reul (2005): Handbook of Stress and the Brain, Teil 1; The Neurobiology of Stress, Volume 15; Elsevier, Seite 624 f

  45. Puglisi-Allegra, Casolini, Angelucci (1991): Changes in brain dopamine and acetylcholine release during and following stress are independent of the pituitary-adrenocortical axis; Brain Research, Volume 538, Issue 1, 4 January 1991, Pages 111-117;

  46. Deutch, Roth (1991): Chapter 19 The determinants of stress-induced activation of the prefrontal cortical dopamine system; Progress in Brain Research, Volume 85, 1991, Pages 367-403;, zitiert nach Steckler, Kalin, Reul (2005): Handbook of Stress and the Brain, Teil 1; Elsevier, Seite 624 f

  47. Deutch, Roth (1991): Chapter 19 The determinants of stress-induced activation of the prefrontal cortical dopamine system; Progress in Brain Research, Volume 85, 1991, Pages 367-403;, zitiert nach Steckler, Kalin, Reul (2005): Handbook of Stress and the Brain, Teil 1; Elsevier, Seite 624 f

  48. Berridge et al (1999), zitiert nach Steckler, Kalin, Reul (2005): Handbook of Stress and the Brain, Teil 1; Elsevier, Seite 811

  49. Anderson, Teicher (1999), Serotonin laterality in amygdala predicts performance in the elevated plus maze in rats, NeuroReport: November 26th, 1999 – Volume 10 – Issue 17 – p 3497–3500

  50. Carlson et al (1993), zitiert nach Steckler, Kalin, Reul (2005): Handbook of Stress and the Brain, Teil 1; Elsevier, Seite 811

  51. Morrow, Gibson, Bagovich, Stein, Condray, Scott (2000): Increased Incidence of Anxiety and Depressive Disorders in Persons With Organic Solvent Exposure; Psychosomatic Medicine: November 2000 – Volume 62 – Issue 6 – p 746-750, zitiert nach Steckler, Kalin, Reul (2005): Handbook of Stress and the Brain, Teil 1; Elsevier, Seite 624 f

  52. Kawahara, Kawahara, Westerink (1999): Comparison of effects of hypotension and handling stress on the release of noradrenaline and dopamine in the locus coeruleus and medial prefrontal cortex of the rat; Naunyn-Schmiedeberg’s Archives of Pharmacology; July 1999, Volume 360, Issue 1, pp 42–49

  53. Goldstein, Rasmusson, Bunney, Roth (1994) The NMDA glycine site antagonist (+)-HA-966 selectively regulates conditioned stress-induced metabolic activation of the mesoprefrontal cortical dopamine but not serotonin systems: a behavioral, neuroendocrine, and neurochemical study in the rat. J Neurosci 14:4937–4950.

  54. Feenstra, Teske, Botterblom, Bruin (1999): Dopamine and noradrenaline release in the prefrontal cortex of rats during classical aversive and appetitive conditioning to a contextual stimulus: interference by novelty effects. Neurosci Lett. 1999 Sep 17;272(3):179-82.

  55. Stahl (2013): Stahl’s Essential Psychopharmacology, 4. Auflage, Chapter 12: Attention deficit hyperactivity disorder and its treatment, Seite 472

  56. Stahl (2013): Stahl’s Essential Psychopharmacology, 4. Auflage, Chapter 12: Attention deficit hyperactivity disorder and its treatment, Seite 476

  57. Stahl (2013): Stahl’s Essential Psychopharmacology, 4. Auflage, Chapter 12: Attention deficit hyperactivity disorder and its treatment, 474

  58. Stahl (2013): Stahl’s Essential Psychopharmacology, 4. Auflage, Seite 472, Chapter 12: Attention deficit hyperactivity disorder and its treatment, 476

  59. Ramos, Arnsten (2007): Adrenergic pharmacology and cognition: focus on the prefrontal cortex. Pharmacol Ther. 2007 Mar; 113(3):523-36., Kapitel 6

  60. Li L, Rana A, Li EM, Feng J, Li Y, Bruchas MR (2023): Activity-dependent constraints on catecholamine signaling. bioRxiv [Preprint]. 2023 Mar 31:2023.03.30.534970. doi: 10.1101/2023.03.30.534970. PMID: 37034631; PMCID: PMC10081217.

  61. Sugama, Takenouchi, Hashimoto, Ohata, Takenaka, Kakinuma (2019): Stress-induced microglial activation occurs through β-adrenergic receptor: noradrenaline as a key neurotransmitter in microglial activation. J Neuroinflammation. 2019 Dec 17;16(1):266. doi: 10.1186/s12974-019-1632-z. PMID: 31847911; PMCID: PMC6916186.

  62. Tennes, Kreye, Avitable, Wells (1986): Behavioral correlates of excreted catecholamines and cortisol in second grade children. J Am Acad Child Psychiatry 25:764–770

  63. Belujon, Grace (2015): Regulation of dopamine system responsivity and its adaptive and pathological response to stress. Proc Biol Sci. 2015 Apr 22;282(1805):20142516. doi: 10.1098/rspb.2014.2516. PMID: 25788601; PMCID: PMC4389605. REVIEW

  64. Oleskevich S, Descarries L, Lacaille JC (1989):. Quantified distribution of the noradrenaline innervation in the hippocampus of adult rat. J Neurosci. 1989 Nov;9(11):3803-15. doi: 10.1523/JNEUROSCI.09-11-03803.1989. PMID: 2585056; PMCID: PMC6569933.

  65. Lipski WJ, Grace AA (2013):Footshock-induced responses in ventral subiculum neurons are mediated by locus coeruleus noradrenergic afferents. Eur Neuropsychopharmacol. 2013 Oct;23(10):1320-8. doi: 10.1016/j.euroneuro.2012.10.007. PMID: 23394871; PMCID: PMC3718869.

  66. Chaouloff (2000): Serotonin, stress and corticoids; Journal of Psychopharmacology, Volume: 14 issue: 2, page(s): 139-151,

  67. Chaouloff, Berton, Mormède (1999): Serotonin and Stress, Neuropsychopharmacology, Volume 21, Issue 2, Supplement 1, 1999, Pages 28S-32S, ISSN 0893-133X,

  68. Quellen hierzu bei den jeweiligen Neurotransmittern / Hormonen

  69. Grandjean, Corcoba, Kahn, Upton, Deneris, Seifritz, Helmchen, Mann, Rudin, Saab (2019): A brain-wide functional map of the serotonergic responses to acute stress and fluoxetine. Nat Commun. 2019 Jan 21;10(1):350. doi: 10.1038/s41467-018-08256-w.

  70. Murnane (2019): Serotonin 2A receptors are a stress response system: implications for post-traumatic stress disorder. Behavioural Pharmacology [09 Jan 2019]; PMID:30632995; DOI: 10.1097/FBP.0000000000000459

  71. Chen, Wang, Zhang, Chu, Mou, Chen (2019): The effects of glucocorticoids on depressive and anxiety-like behaviors, mineralocorticoid receptor-dependent cell proliferation regulates anxiety-like behaviors, Behavioural Brain Research, 2019, ISSN 0166-4328,

  72. Keeney, Jessop, Harbuz, Marsden, Hogg, Blackburn‐Munro (2006): Differential Effects of Acute and Chronic Social Defeat Stress on Hypothalamic‐Pituitary‐Adrenal Axis Function and Hippocampal Serotonin Release in Mice. Journal of Neuroendocrinology, 18: 330-338. doi:10.1111/j.1365-2826.2006.01422.x

  73. Liu, Aghajanian (2008): Stress blunts serotonin- and hypocretin-evoked EPSCs in prefrontal cortex: Role of corticosterone-mediated apical dendritic atrophy; Proceedings of the National Academy of Sciences Jan 2008, 105 (1) 359 364; DOI:10.1073/pnas.0706679105

  74. Kawahara, Yoshida, Yokoo, Nishi, Tanaka (1993): Psychological stress increases serotonin release in the rat amygdala and prefrontal cortex assessed by in vivo microdialysis, Neuroscience Letters, Volume 162, Issues 1–2, 1993, Pages 81-84, ISSN 0304-3940,

  75. Korte‐Bouws, G. A., Korte, S. M., De Kloet, E. R. and Bohus, B. (1996), Blockade of Corticosterone Synthesis Reduces Serotonin Turnover in the Dorsal Hippocampus of the Rat as Measured by Microdialysis. Journal of Neuroendocrinology, 8: 877-881. doi:10.1046/j.1365-2826.1996.05389.x

  76. Evrard, Barden, Hamon, Adrien (2006): Glucocorticoid Receptor-Dependent Desensitization of 5-HT1A Autoreceptors by Sleep Deprivation: Studies in GR-i Transgenic Mice. Sleep. 29. 31-6. 10.1093/sleep/29.1.31.

  77. Le Poul, Laaris, Hamon, Lanfumey (1997): Fluoxetine‐induced desensitization of somatodendritic 5‐HT1A autoreceptors is independent of glucocorticoid(s). Synapse, 27: 303-312. doi:10.1002/(SICI)1098-2396(199712)27:4<303::AID-SYN4>3.0.CO;2-G

  78. Popova, Naumenko (2019): Neuronal and behavioral plasticity: the role of serotonin and BDNF systems tandem. Expert Opin Ther Targets. 2019 Jan 21. doi: 10.1080/14728222.2019.1572747.

  79. Hood, Hince, Robinson, Cirillo, Christmas, Kaye (2006): Serotonin regulation of the human stress response, Psychoneuroendocrinology, Volume 31, Issue 9, 2006, Pages 1087-1097, ISSN 0306-4530,

  80. Yehuda, Meyer (1984): A Role for Serotonin in the Hypothalamic-Pituitary-Adrenal Response to Insulin Stress. Neuroendocrinology 1984;38:25-32. doi: 10.1159/000123861

  81. Seedat, Stein, Ziervogel, Middleton, Kaminer, Emsley, Rossouw (2002): Comparison of Response to a Selective Serotonin Reuptake Inhibitor in Children, Adolescents, and Adults with Posttraumatic Stress Disorder; Journal of Child and Adolescent Psychopharmacology 2002 12:1, 37-46; n = 38

  82. Reimold, Knobel, Rapp, Batra, Wiedemann, Ströhle, Zimmer, Schönknecht, Smolka, Weinberger, Goldman, Machulla, Bares (2011): Central serotonin transporter levels are associated with stress hormone response and anxiety; Psychopharmacology, February 2011, Volume 213, Issue 2–3, pp 563–572, n = 40

  83. Way, Taylor (2010): The Serotonin Transporter Promoter Polymorphism Is Associated with Cortisol Response to Psychosocial Stress, Biological Psychiatry, Volume 67, Issue 5, 2010, Pages 487-492, ISSN 0006-3223, n = 182

  84. Mueller, Brocke, Fries, Lesch, Kirschbaum (2010): The role of the serotonin transporter polymorphism for the endocrine stress response in newborns, Psychoneuroendocrinology, Volume 35, Issue 2, 2010, Pages 289-296, ISSN 0306-4530, n = 126

  85. Mueller, Armbruster, Moser, Canli, Lesch, Brocke, Kirschbaum (2011): Interaction of Serotonin Transporter Gene-Linked Polymorphic Region and Stressful Life Events Predicts Cortisol Stress Response; Neuropsychopharmacology volume 36, pages 1332–1339, 2011, n = 320

  86. Ouellet-Morin, Wong, Danese, Pariante, Papadopoulos, Mill, Arseneault (2013): Increased serotonin transporter gene (SERT) DNA methylation is associated with bullying victimization and blunted cortisol response to stress in childhood: a longitudinal study of discordant monozygotic twins; Psychological Medicine; Volume 43, Issue 9 September 2013 , pp. 1813-1823;

  87. Christoffersen (2019): Violent crime against children with disabilities: A nationwide prospective birth cohort-study. Child Abuse Negl. 2019 Sep 24;98:104150. doi: 10.1016/j.chiabu.2019.104150.

  88. Canli, Qiu, Omura, Congdon, Haas, Amin, Herrmann, Constable, Lesch (2006): Neural correlates of epigenesis; Proc Natl Acad Sci U S A. 2006 Oct 24; 103(43): 16033–16038. doi: 10.1073/pnas.0601674103; PMCID: PMC1592642; PMID: 17032778

  89. Caspi, Sugden, Moffitt, Taylor, Craig, Harrington, McClay, Mill, Martin, Braithwaite, Poulton (2003): Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science. 2003 Jul 18;301(5631):386-9.

  90. Alexander, Kuepper, Schmitz, Osinsky, Kozyra, Hennig (2009): Gene-environment interactions predict cortisol responses after acute stress: implications for the etiology of depression. Psychoneuroendocrinology. 2009 Oct;34(9):1294-303. doi: 10.1016/j.psyneuen.2009.03.017.

  91. Diamond (2014): Biologische und soziale Einflüsse auf kognitive Kontrollprozesse, die vom präfrontalen Kortex abhängen; In: Kubesch (Herausgeberin): Exekutive Funktionen und Selbstregulation – Neurowissenschaftliche Grundlagen und Transfer in die pädagogische Praxis; Huber, Seite 30

  92. Cools, D’Esposito (2011): Inverted-U shaped dopamine actions on human working memory and cognitive control; Biol Psychiatry. 2011 Jun 15; 69(12): e113–e125. doi: 10.1016/j.biopsych.2011.03.028; PMCID: PMC3111448; NIHMSID: NIHMS286132;

  93. Castellanos, Tannock (2002): Neuroscience of attention-deficit/hyperactivity disorder: The search for endophenotypes; Article in Nature reviews Neuroscience 3(8):617-28 · September 2002; DOI: 10.1038/nrn896, S. 621 mwNw

  94. Krause und Krause (2014): ADHS im Erwachsenenalter; Symptome – Differentialdiagnose – Therapie; S. 267

  95. Mattay, Goldberg, Fera, Hariri, Tessitore, Egan, Kolachana, Callicott, Weinberger (2003): Catechol O-methyltransferase val158-met genotype and individual variation in the brain response to amphetamine; doi: 10.1073/pnas.0931309100; PNAS May 13, 2003 vol. 100 no. 10 6186-6191

  96. Zahrt, Taylor, Mathew, Arnsten (1997): Supranormal stimulation of D1 dopamine receptors in the rodent prefrontal cortex impairs spatial working memory performance. J Neurosci. 1997 Nov 1;17(21):8528-35.

  97. Arnsten, Cai, Murphy, Goldman-Rakic (1994): Dopamine D1 receptor mechanisms in the cognitive performance of young adult and aged monkeys. Psychopharmacology (Berl). 1994 Oct;116(2):143-51.

  98. Arnsten (2006): Stimulants: Therapeutic Actions in ADHD; Neuropsychopharmacology 2006 31, 2376–2383. doi:10.1038/sj.npp.1301164

  99. Cai, Arnsten (1994): Dose-dependent effects of the dopamine D1 receptor agonists A77636 or SKF81297 on spatial working memory in aged monkeys. J Pharmacol Exp Ther. 1997 Oct;283(1):183-9.

  100. Gibbs, D’Esposito (2005): Individual capacity differences predict working memory performance and prefrontal activity following dopamine receptor stimulation Cognitive, Affective, & Behavioral Neuroscience (2005) 5: 212.

  101. Lidow, Koh, Amsten (2003). D1 dopamine receptors in the mouse prefrontal cortex: Immunocytochemical and cognitive neuropharmacological analyses. Synapse, 47, 101- 108.

  102. Vijayraghavan, Wang, Birnbaum, Williams, Arnsten (2007): Inverted-U dopamine D1 receptor actions on prefrontal neurons engaged in working memory. Nat Neurosci. 2007 Mar;10(3):376-84.

  103. Stahl (2013): Stahl’s Essential Psychopharmacology, 4. Auflage, Chapter 12: Attention deficit hyperactivity disorder and its treatment, Seite 477

  104. Stahl (2013): Stahl’s Essential Psychopharmacology, 4. Auflage, Chapter 12: Attention deficit hyperactivity disorder and its treatment, Seite 488

  105. Poltavski, Petros (2006): Effects of transdermal nicotine on attention in adult non-smokers with and without attentional deficits. Physiol Behav. 2006 Mar 30;87(3):614-24.

  106. Abercrombie, Keefe, DiFrischia, Zigmond (1989): Differential Effect of Stress on In Vivo Dopamine Release in Striatum, Nucleus Accumbens, and Medial Frontal Cortex. Journal of Neurochemistry, 52: 1655–1658; doi:10.1111/j.1471

  107. ohne Zahlenangaben: Finlay, Zigmond (1997): The effects of stress on central dopaminergic neurons: possible clinical implications. Neurochem Res. 1997 Nov;22(11):1387-94.

  108. Heinz (2000/2013): Das dopaminerge Verstärkungssystem; Seite 105, mit weiteren Nachweisen; die Ausgabe 2013 scheint gegenüber derjenigen von 2000 unverändert

  109. Arnsten, Contant (1992): a-2 adrenergic agonists decrease distractibility in aged monkeys performing the delayed response task. Psychopharmacology 108, 159-169.

  110. Arnsten, Leslie (1991): Behavioral and receptor binding analysis of the a-2 adrenergic agonist, UK-14304 (5 bromo-6 2-imidazoline-2-yl amino quinoxaline): Evidence for cognitive enhancement at an a-2 adrenoceptor subtype. Neuropharmacology 30, 1279-1289.

  111. Arnsten, Cai, Goldman-Rakic (1988): The a-2 adrenergic agonist guanfacine improves memory in aged monkeys without sedative or hypotensive side effects: Evidence for a-2 receptor subtypes. J. Neurosci. 8, 4287-4298

  112. Cai, Ma, Xu, Hu, (1993): Resperine impairs spatial working memory performance in monkeys: Reversal by the a-2 adrenergic agonist clonidine. Brain Res. 614, 191-196

  113. Skosnik, Chatterton, Swisher, Park (2000): Modulation of attentional inhibition by norepinephrine and cortisol after psychological stress; International Journal of Psychophysiology 36 2000 59-68

  114. Birnbaum, Gobeske, Auerbach, Taylor, Arnsten (1999): A role for norepinephrine in stress-induced cognitive deficits: α-1-adrenoceptor mediation in prefrontal cortex. Biol. Psychiatry 46, 1266–1274.

  115. Ramos, Colgan, Nou, Ovadia, Wilson, Arnsten (2005). The beta-1 adrenergic antagonist, betaxolol, improves working memory performance in rats and monkeys. Biol. Psychiatry 58, 894–900.

  116. Arnsten, Scahill, Findling (2007): alpha2-Adrenergic receptor agonists for the treatment of attention-deficit/hyperactivity disorder: emerging concepts from new data. J Child Adolesc Psychopharmacol 2007;17:393–406.

  117. ähnlich: Arnsten (2000): Stress impairs prefrontal cortical function in rats and monkeys: role of dopamine D1 and norepinephrine alpha-1 receptor mechanisms. Prog Brain Res. 2000;126:183-92.

  118. Für starke Stimulation des D1-Dopaminrezeptors: Zahrt, Taylor, Mathew, Arnsten (1997): Supranormal stimulation of D1 dopamine receptors in the rodent prefrontal cortex impairs spatial working memory performance. J Neurosci. 1997 Nov 1;17(21):8528-35.

  119. Kao, Stalla, Stalla, Wotjak, Anderzhanova (2015): Norepinephrine and corticosterone in the medial prefrontal cortex and hippocampus predict PTSD-like symptoms in mice. Eur J Neurosci, 41: 1139–1148. doi:10.1111/ejn.12860

  120. Dietrich (2010): Aufmerksamkeitsdefizit-Syndrom, Schattauer

  121. Mobbs, Petrovic, Marchant, Hassabis, Weiskopf, Seymour, Dolan, Frith (2007): When fear is near: threat imminence elicits prefrontal-periaqueductal gray shifts in humans. Science. 2007 Aug 24;317(5841):1079-83.

  122. Shansky, Lipps (2013): Stress-induced cognitive dysfunction: hormone-neurotransmitter interactions in the prefrontal cortex. Front. Hum. Neurosci. 7, 123.

  123. Vogel, Fernández, Joëls, Schwabe (2016): Cognitive Adaptation under Stress: A Case for the Mineralocorticoid Receptor DOI: OPINION, VOLUME 20, ISSUE 3, P192-203, MARCH 01, 2016

  124. Wagner, Born: Psychoendokrine Aspekte neurophysiologischer Funktionen. In: Lautenbacher, Gauggel (2013): Neuropsychologie psychischer Störungen, Springer, Seite 131

  125. McEwen, Sapolsky (1995): Stress and cognitive function. Curr. Opin. Neurobiol. 5, 205-216.

  126. Arnsten (2020): Guanfacine’s mechanism of action in treating prefrontal cortical disorders: Successful translation across species. Neurobiol Learn Mem. 2020 Dec;176:107327. doi: 10.1016/j.nlm.2020.107327. PMID: 33075480; PMCID: PMC7567669.

  127. Ramos, Arnsten (2007): Adrenergic pharmacology and cognition: focus on the prefrontal cortex. Pharmacol Ther 2007;113:523–536.

  128. Aston-Jones, Cohen (2005): An integrative theory of locus coeruleus-norepinephrine function: adaptive gain and optimal performance. Annu Rev Neurosci 2005;28:403–450.

  129. Aston-Jones, Cohen (2005): Adaptive gain and the role of the locus coeruleus-norepinephrine system in optimal performance. J Comp Neurol 2005;493:99–110.

  130. Kobori, Moore, Dash (2015): Altered regulation of protein kinase a activity in the medial prefrontal cortex of normal and brain-injured animals actively engaged in a working memory task. J Neurotrauma. 2015 Jan 15;32(2):139-48. doi: 10.1089/neu.2014.3487. Epub 2014 Nov 13. PMID: 25027811; PMCID: PMC4291093.

  131. Kauser, Sahu, Kumar, Panjwani (2013); Guanfacine is an effective countermeasure for hypobaric hypoxia-induced cognitive decline. Neuroscience. 2013 Dec 19;254:110-9. doi: 10.1016/j.neuroscience.2013.09.023. PMID: 24056194.

  132. Al-Damluji (1988): Adrenergic mechanisms in the control of corticotrophin secretion. J Endocrinol 1988;119:5–14.

  133. Plotsky, Cunningham, Widmaier (1989): Catecholaminergic modulation of corticotropin-releasing factor and adrenocorticotropin secretion. Endocr Rev 1989;10:437–458.

  134. Dunn, Swiergiel, Palamarchouk (2004): Brain circuits involved in corticotropin-releasing factor-norepinephrine interactions during stress. Ann N Y Acad Sci 2004;1018:25–34.

  135. Schinke, Hesse, Rullmann, Becker, Luthardt, Zientek, Patt, Stoppe, Schmidt, Meyer, Meyer, Orthgieß, Blüher, Kratzsch, Ding, Then Bergh, Sabri (2018): Central noradrenaline transporter availability is linked with HPA axis responsiveness and copeptin in human obesity and non-obese controls. Stress. 2018 Oct 29:1-10. doi: 10.1080/10253890.2018.1511698.

  136. Hupalo, Berridge (2016): Working Memory Impairing Actions of Corticotropin-Releasing Factor (CRF) Neurotransmission in the Prefrontal Cortex. Neuropsychopharmacology. 2016 Oct;41(11):2733-40. doi: 10.1038/npp.2016.85.


  138. Lee, Shin, Stein (2010): Increased Cortisol after Stress is Associated with Variability in Response Time in ADHD Children; Yonsei Med J. 2010 Mar;51(2):206-211. English.

  139. Wheelock, Harnett, Wood, Orem, Granger, Mrug, Knight (2016): Prefrontal Cortex Activity Is Associated with Biobehavioral Components of the Stress Response. Front Hum Neurosci. 2016 Nov 17;10:583. eCollection 2016.

  140. Steinhausen, Rothenberger, Döpfner (2010): Handbuch ADHS, Seite 83

  141. Berridge, Robinson (1998): What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience? Brain Res Brain Res Rev. 1998 Dec;28(3):309-69

  142. Heinz (2000): Das dopaminerge Verstärkungssystem – Funktion, Interaktion mit anderen Neurotransmittern und psychopathologische Korrelate; Monografien aus dem Gesamtgebiet der Psychiatrie, Seite 10

  143. Trott, Wirth (2000): die Pharmakotherapie der hyperkinetischen Störungen; in: Steinhausen (Herausgeber) Hyperkinetische Störungen bei Kindern, Jugendlichen und Erwachsenen, 2. Aufl., Seite 215

  144. Zigmond, Hastings, Abercrombie (1992): Neurochemical Responses to 6‐Hydroxydopamine and L‐Dopa Therapy: Implications for Parkinson’s Diseasea. Annals of the New York Academy of Sciences, 648: 71-86. doi:10.1111/j.1749-6632.1992.tb24525.x

  145. Zhang, Tarazi, Baldessarini (2001): Role of Dopamine D4 Receptors in Motor Hyperactivity Induced by Neonatal 6-Hydroxydopamine Lesions in Rats; Neuropsychopharmacology (2001) 25, 624–632. doi:10.1016/S0893-133X(01)00262-7

  146. Hässler, Irmisch: Biochemische Störungen bei Kindern mit AD(H)S, Seite 87, in Steinhausen (Hrsg.) (2000): Hyperkinetische Störungen bei Kindern, Jugendlichen und Erwachsenen, 2. Aufl., Kohlhammer

  147. Scheidtmann (2010): Bedeutung der Neuropharmakologie für die Neuroreha – Wirkung von Medikamenten auf Motivation und Lernen; neuroreha 2010; 2(2): 80-85; DOI: 10.1055/s-0030-1254343

  148. Solanto (1998): Neuropsychopharmacological mechanisms of stimulant drug action in attention-deficit hyperactivity disorder: a review and integration; Behav Brain Res. 1998 Jul;94(1):127-52.

  149. Pomerleau, Downey, Stelson, Pomerleau (1995): Cigarette Smoking in Adult Patients Diagnosed with Attention Deficit Hyperactivity Disorder; journal of Substance Abuse, 7,373-378 (1995) BRIEF REPORT

  150. Kilgus (2007):Selbstregulation der langsamen kortikalen Potentiale bei Kindern mit und ohne ADHS (Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung) – Eine Pilotstudie -. Dissertation, Seite 3

  151. Pontieri, Tanda, Orzi, Chiara (1996): Effects of nicotine on the nucleus accumbens and similarity to those of addictive drugs. Nature. 1996 Jul 18;382(6588):255-7.

  152. Chishti, Fisher, Seegal (1996): Aroclors 1254 and 1260 reduce dopamine concentrations in rat striatal slices. Neurotoxicology. 1996 Fall-Winter;17(3-4):653-60.

  153. Koob, Le Moal (2001): Drug addiction, dysregulation of reward, and allostasis; Neuropsychopharmacology. 2001 Feb;24(2):97-129, zitiert nach Riederer, Laux (2009): Neuro-Psychopharmaka. Ein Therapie-Handbuch: Band 6: Notfalltherapie, Antiepileptika, Psychostimulantien, Suchttherapeutika und sonstige Psychopharmaka, Springer-Verlag, Seite 306

  154. Trott, Wirth (2000): die Pharmakotherapie der hyperkinetischen Störungen; in: Steinhausen (Herausgeber) hyperkinetischen Störungen bei Kindern, Jugendlichen und Erwachsenen, 2. Aufl., Seite 214, mwNw.


  156. Cossu (2014): Therapeutic options to enhance coma arousal after traumatic brain injury: State of the art of current treatments to improve coma recovery; British Journal of Neurosurgery; Volume 28, 2014 – Issue 2 Pages 187-198;

  157. Chang, Grace (2013): Amygdala β-noradrenergic receptors modulate delayed downregulation of dopamine activity following restraint. J Neurosci. 2013 Jan 23;33(4):1441-50. doi: 10.1523/JNEUROSCI.2420-12.2013.

  158. Stahl (2013): Stahl’s essential psychopharmacology, 4. Ausgabe, Chapter 12: Attention deficit hyperactivity disorder and its treatment, Seite 488

Diese Seite wurde am 21.02.2024 zuletzt aktualisiert.