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Neurophysiological correlates of stress

Neurophysiological correlates of stress

Stress correlates with specific neurophysiological patterns. The changes in neurotransmitters and other messenger substances explain behavioral changes caused by stress.

Our hypothesis is that ADHD causes a disorder of the stress regulatory systems in which the stress systems are persistently activated (ADHD-HI, ADHD-C) or overreact (ADHD-I) in the absence of an adequate stressor. At the very least, ADHD mediates its symptoms in the same or a very similar way as chronic stress, namely through decreased dopamine and norepinephrine.
We consider almost all ADHD symptoms to be functional stress symptoms, i.e., regular consequences of activation of the stress systems as they were useful for survival in a life-threatening situation (in the last millions of years).

If our hypothesis that ADHD causes a sustained activation of the stress systems is correct, the same neurophysiological changes in the brain should be found in the literature on (severe) stress responses as on ADHD symptoms. To verify this, in this paper we collect the neurophysiological correlates of stress as they emerge from the relevant scientific literature on stress.

As a result, we can conclude that the neurophysiological correlates of ADHD are impressively similar to the neurophysiological correlates of chronic stress, especially chronic social stress in adolescence
In contrast, acute short-term stress has divergent neurophysiological patterns.

Which stressors trigger which stress responses in an individual through which (neuronal/neurobiological) pathway depends on genes, epigenetic changes, and environmental factors.1
Stress shows very different consequences depending on the duration, type of stressor, whether it is existing or feared, gender and age of the individual.
See more at Stress timing determines type of mental disorder And Type of stress determines location of neurological changes in the article Stress damage caused by early/long-term stress.

This paper was originally based on an article by Arnsten (2009).2

1. PFC

Basically, a distinction must be made between the consequences of acute and chronic stress. While acute stress increases dopamine and norepinephrine levels in the PFC, chronic stress decreases dopamine levels in the PFC. Increases as well as decreases in dopamine and noradrenaline levels impair working memory.

Early childhood stress can decrease or increase dopamine in the PFC.3

1.1. Types of stress

1.1.1. Acute severe stress

Stress impairs processes of the PFC that support goal-directed behavior, but arguably not processes of the oPFC4 such as reversal learning.
While in the non-stress state the PFC can control its own norepinephrine and dopamine levels to function optimally, during acute stress the amygdala via the hypothalamus and midbrain (mesencephalon, part of the brainstem) raise dopamine5 and norepinephrine levels to such an extent that PFC function is impaired.267

Acute stress increases dopamine output from the ventral tegmentum, which increases dopamine levels in the PFC, basolateral amygdala, and nucleus accumbens. The mPFC inhibits the nucleus accumbens, whereas the amygdala inhibits the PFC and activates the nucleus accumbens. If the inhibitory effect of the PFC on the nucleus accumbens is lost due to excessively high dopamine levels, severe stress symptoms occur.8

If (e.g., during acute stress) D1 receptors are activated too strongly, this increases cAMP, which inhibits the overall task-directed firing of neurons in all directions of the PFC network and impairs working memory.8 This can be prevented by appropriate administration of D1 antagonists,9 cAMP inhibitors, or PKA inhibitors10 in the PFC. Dopamine and norepinephrine receptors are closely associated with the cAMP-PKA pathway.11
High doses of D1/D5 antagonists or D1/D5 agonists equally impair working memory; mild doses improve working memory.12

According to one account, the dopamine level between the PFC and the striatum is rigidly inversely proportional to each other: a high dopamine level in the PFC correlates with a low dopamine level in the striatum and vice versa.1314 According to another account, a lack of dopamine in the right mPFC leads to a likewise reduced dopamine level in the nucleus accumbens of the striatum.15 This model may better explain ADHD associated with decreased dopamine levels in the PFC and striatum.

Stress changes the brain’s response patterns from slow, reasoned control by the PFC to reflexive and rapid emotional control by the amygdala and related subcortical structures.2

Acute, uncontrollable stress impairs PFC-mediated cognitive functions in humans and animals and shifts behavioral and emotional control to more primitive posterior brain circuits.2

Glucocorticoid and dopamine receptors interact in relation to stress in the PFC. During stress, glucocorticoids are released by the HPA axis, which cross the blood-brain barrier and address glucocorticoid receptors throughout the brain.16

  • Glucocorticoids given directly into the PFC increase dopamine levels in the PFC and enhance stress-induced impairments in executive functions of the PFC. Conversely, glucocorticoid antagonists given into the PFC decrease stress-induced dopamine levels in the PFC.17 Similarly, activation of the HPA axis stimulates the ventral tegmentum, which like the PFC has many glucocorticoid receptors, and correlates with an increase in dopamine in the PFC.18 Because glucocorticoid administration to the ventral tegmentum does not increase dopamine levels in the PFC during stress, it does not appear to be directly controlled by the ventral tegmentum.
    High levels of cortisol in the blood also impair working memory, but not declarative memory.19
  • The glucocorticoid corticosterone blocks the glial cell-based dopaminergic OTC2 transporters in the PFC, which remove dopamine from the synaptic cleft. As a result, corticosterone increases extracellular dopamine levels.2021

As a result, glucocorticoids released by stress in the PFC may cause overstimulation of D1 receptors, thereby contributing to PFC shutdown.

Insofar as, as we hypothesize, the cortisol stress response is often exaggerated in ADHD-I (without hyperactivity) and the cortisol stress response tends to be flattened in ADHD-HI (with hyperactivity), this should result in working memory problems being somewhat less severe in ADHD-HI.
Since tonic dopamine levels in the PFC are reduced in ADHD due to chronic stress, a stronger cortisol stress response that increases dopamine levels should, in aggregate, result in a lesser dopamine reduction in the PFC. Put another way, the exaggerated phasic dopamine and norepinephrine stress response might compensate a little for the tonic dopamine and norepinephrine deficit-but the timing must be taken into account, since the cortisol stress response occurs about 20 minutes after the stressor. As a result, ADHD-I would be expected to show slightly less impairment in executive functions than ADHD-HI.
At least this is consistent with the results of our online test. Out of about 1400 participants, those who reported having ADHD-I had slightly lower symptom severity overall than those who reported being from ADHD-HI/ADHD-C. ADHD-HI consistently had more severe symptoms than ADHD-I in all symptom domains, i.e., even outside of hyperactive/impulsive symptomatology. In particular, ADHD-HI sufferers also reported thinking blocks and decision-making difficulties more frequently or more severely than ADHD-I sufferers.

1.1.2. Chronic severe stress Dopamine reduction due to chronic stress Dopamine reduction in the PFC due to chronic stress

Chronic stress over 4 weeks caused decreased dopamine levels in the PFC in rats, which impaired working memory.22
The changes triggered by 4 weeks of chronic stress (depressive behavior, a negative feedback resistance in the dexamethasone suppression test, decrease in extracellular dopamine in the PFC) remained 3 months later.23 Only the decrease in extracellular serotonin in the PFC had regressed by then
Several other studies confirm that chronic stress reduces dopamine levels in the PFC. Chronic stress in adolescence reduces dopamine levels in the PFC not only in adolescence but also throughout adulthood.24

Chronic stress increased norepinephrine transporters in the PFC, whereas norepinephrine levels remained unchanged.25
Noradrenaline transporters primarily reabsorb dopamine in the PFC. Increased noradrenaline transporters thus cause decreased dopamine levels.26

Stress during birth appears to decrease basal dopamine levels in the PFC while increasing them in the nucleus accumbens as well as in the striatum,27 for example, oxygen deprivation during birth.2829

Prenatal stress may laterally affect dopamine levels in the PFC.30 In ADHD, the basal dopamine level is decreased in the right hemisphere of the PFC, whereas in the aforementioned experiment it was increased right hemispherically in the PFC.

When rat mothers were administered glucocorticoids in the last trimester of pregnancy, the offspring showed decreased dopamine levels in the nucleus accumbens and other mesolimbic structures, an altered ratio of dopamine D1 to D2 receptors, and an addictive tendency.3 Another study also found an addictive tendency after prenatal stress.31

Repetitive social stress in youth comparable to bullying caused decreased dopamine levels in the PFC in adult rodents through increased D2 reuptake and increased dopamine degradation.32 Social stress in youth increased the activity of DAT, which degrades dopamine.33 Repeated social stress in youth decreased D2 receptors in adulthood,34 whereas social isolation in youth increased D2 receptors in adulthood.35 Repeated social stress over 5 days in juvenile rodents decreased dopamine levels in adult mPFC3637 and increased norepinephrine and serotonin levels in the ventral dentate gyrus and decreased norepinephrine levels in the dorsal raphe nuclei.36
The reduction in mPFC dopamine levels in adulthood may also be caused by repeated pharmacological activation of D2 autoreceptors in the mPFC during the same juvenile period.37

Chronic defense stress in mice revealed two differently sensitive groups. Increased expression of D2S, D2L, and D2R receptor dimers in the PFC was observed in both groups. Significantly decreased D2S receptor mRNA expression was seen in the amygdala.38 Dopamine reduction in the striatum due to chronic stress

Prolonged (one-time) stress, as used to provoke PTSD in rodents, decreased dopamine levels and D2 receptors in the striatum and increased DAT in the striatum. D1 receptors in the striatum remained unchanged.39 It further decreased dopamine in the infralimbic cortex.40 Reduction of dopaminergic cells in substantia nigra by chronic stress

Chronic movement impairment (restraint) of rodents (8 of 24 hours on 5 of 7 days) caused a loss of dopaminergic cells in the substantia nigra of up to 61% after 16 weeks, increasing with duration. Similarly, noradrenergic cells in the locus coeruleus were reduced. At the same time, there was a marked increase in activation of microglia and an increase in nitrotyrosine in the substantia nigra and locus coeruleus. This suggests oxidative stress, which could trigger the decrease in dopaminergic and noradrenergic cells.41 Other effects of chronic stress Reduction of noradrenergic cells in the nucleus coeruleus due to chronic stress

Chronic movement impairment (restraints) of rodents (8 of 24 hours on 5 of 7 days) reduced noradrenergic cells in the locus coeruleus, as did a loss of dopaminergic cells in the substantia nigra that increased with duration.41

A unique long-lasting stressor, as used to induce PTSD, induced in rat noradrenergic cells of the locus coeruleus42

  • Lower spontaneous activity but higher evoked responses, resulting in an increased signal-to-noise ratio of locus coeruleus neurons
  • Impaired recovery after stimulation inhibition.
  • An excessive tyrosine hydroxylase mRNA expression in the locus coeruleus

A comprehensive study of several types of stress as one-time or prolonged stressors found in rats:43

  • One-time stressors had a different effect depending on the stressor
    • Immobilization stress
      • Increased tyrosine hydroxylase mRNA expression
        • In brainstem A1, A2, A5 and locus coeruleus
      • Unmodified NET mRNAs and VMAT2 mRNAs
    • Glycolysis inhibition by 2-deoxy-D-glucose
      • Increased tyrosine hydroxylase mRNA expression
        • In brainstem A1, A2, A5 and locus coeruleus
      • Unmodified NET mRNAs and VMAT2 mRNAs
    • Cold
      • Increased tyrosine hydroxylase mRNA expression
        • In brainstem A2 and locus coeruleus
      • Unmodified NET mRNAs and VMAT2 mRNAs
    • Insulin
      • Unchanged tyrosine hydroxylase mRNA expression
      • Unmodified NET mRNAs and VMAT2 mRNAs
  • Chronic stress had a different effect depending on the stressor
    • Immobilization stress, 2 hours daily for 41 days
      • Increased tyrosine hydroxylase mRNA expression
        • Same increase as from one-time immobilization
          • In brainstem A1, A2, A5 and
        • Increase lower than due to one-time immobilization
          • In locus coeruleus
        • Further enhancement of increased tyrosine hydroxylase mRNA expression by single cold stress or 2-deoxy-D-glucose
          • Only in locus coeruleus
        • No change due to new one-time immobilization
      • Increased NET mRNAs and VMAT2 mRNAs
        • Only in brainstem A1- and A2
    • Glycolysis inhibition by 2-deoxy-D-glucose
      • Increased tyrosine hydroxylase mRNA expression
        • In brainstem A1, A2, A5 and locus coeruleus
    • Cold
      • Increased tyrosine hydroxylase mRNA expression
        • Only in brainstem A2 and lucus coeruleus
    • Insulin
      • No increased tyrosine hydroxylase mRNA expression Altered phosphorylation and oxidative stress

Chronic stress (electric foot shocks) in mice

  • Decreased the phosphorylation of Extracellular-signal Regulated Kinase (ERK1 / 2) and
  • Decreased the phosphorylation of cyclic AMP-responsive element binding protein (CREB-1),
  • Increased the phosphorylation of the N-methyl-d-aspartate (NMDA) receptor (type 1) in the hippocampus

These effects were prevented by administration of (-)-sesamin (a polyphenol found in sesame oil, among others) prior to stress.44

1.1.3. Mild stress

Mild acute stress exposure does not impair, and may even enhance, memory consolidation by the hippocampus and amygdala. The vmPFC regulates fear responses mediated by the amygdala 8 45
In contrast, more severe acute stressors impair hippocampal functions but continue to strengthen amygdala and striatum emotional motor functions.

Mild stress, such as when the mother returns after brief separation, promotes stress processing in adulthood and reduces impulsivity and basal HPA axis stress hormones in the blood.46. Baby rats that were repeatedly removed from their mothers for only a short period of time, or taken in hand, showed a lower HPA axis response to stress in adulthood by increasing glucocorticoid receptor (GR) expression in the PFC and hippocampus. GR are the receptors through which cortisol (corticosterone in rodents) shuts down the HPA axis at the end of the stress response. In contrast, during prolonged maternal withdrawal, endotoxin administration, or trauma inducing severe or chronic stress, HPA axis sensitivity was increased in adulthood47 and GR expression was decreased in the dlPFC (and, to a much lesser extent, in the ventrolateral PFC).48 The mineralocorticoid receptors (MR) (which have a much higher affinity for corticosteroids and control the diurnal cycle) remained unchanged, which worsened the MR to GR ratio. If stress occurred only in adulthood, the expression of GR in CA1 of the hippocampus and of MR in the ventrolateral PFC decreased instead.

Chronic mild stress is associated by the preponderant literature with depressive response patterns linked to underactivity of the mesolimbic dopamine system and increased binding to cortical beta-adrenergic receptors. For a smaller group, an aberrant response to chronic mild stress is described, linked to increased activity of the mesolimbic dopamine system and decreased binding to cortical beta-adrenergic receptors.49 It would be interesting to know whether these are subtypes of melancholic depression and atypical depression.

1.2. Behavioral effects of stress in the PFC

1.2.1. Attention

Stress alters attentional control.2 Here, attentional regulation changes from top-down control by the PFC prioritizing relevance for goal attainment to stimulus-prioritized bottom-up control by sensory cortices. Attentional control thus switches from a volitional control by the PFC to an automatic response to stimuli by posterior brain regions.50
This corresponds quite closely to the change in attentional control in ADHD.

Stress impaired selective attention in an animal experiment only when it was uncontrollable.2

Stress impairs attentional control and connectivity within a frontoparietal network that mediates attentional switching (task switching).51
Task changes are controlled by the mPFC.52

Stress impairs task switching, which correlates with a decrease in apical dendritic spines in mPFC.53

In ADHD, attentional control is altered in precisely this specific way: in ADHD, neither attention itself nor the directability of attention per se is impaired; rather, attentional control is subject to its own specific pattern: task switching is impeded, distraction is facilitated. Attention is increasingly subject to intrinsic control.

1.2.2. Working memory

Stress impairs working memory in the dlPFC2 and increases conditioning for negative but not positive stimuli54 and default mode network activity.55

The working memory

Working memory is tested by tests in which information received must be retained during a delay in order to make a decision after the delay has ended. Monkeys are asked to remember the position of a briefly presented stimulus on a screen and then move their eyes to focus on that position. Rodents are asked to remember which arm of a T-shaped maze it visited previously and visit the opposite arm on the following trial. The tasks are repeated tens or hundreds of times, so that during the delay not only the “signal” (i.e., the correct choice) must be kept in memory, but also the “noise” (information from previous trials) must be suppressed
Certain neurons of the PFC are active only during this delay.56 Lesions of the PFC affect the accuracy of decisions only with respect to tasks that involve delay and the longer the delay, the more severely.57 Consequently, the PFC is not involved in the motor or motivational task parts. Working memory function requires moderate neurotransmitter levels in the PFC, which are altered by stress.18 Acute high stress deactivates working memory via norepinephrine

Working memory requires an intermediate level of norepinephrine for optimal function. Norepinephrine levels that are too low or too high impair working memory. This control occurs by means of different affinity norepinephrine receptors: the high-affinity α2-adrenergic receptors and the lower affinity α1- and β-adrenergic receptors.58596061626364 This control mechanism corresponds to the shutdown of the HPA axis after stress response by cortisol by means of the high-affinity mineralocorticoid receptors and the low-affinity glucocorticoid receptors.
The absence of norepinephrine thus calms the PFC and enables sleep. Norepinephrine in moderate doses activates working memory and increases cognitive performance. High levels of norepinephrine during stress impair working memory and thus cognitive flexibility. Stimulation of α1- and β-adrenergic receptors by very high levels of norepinephrine not only impairs (spatial) working memory but also increases the activity of posterior and subcortical functions that take over behavioral control instead of the PFC during stress.5865 α1-Receptor antagonists prevent the impairment of the PFC by stress.66 In practice, α1-adrenoceptor antagonists are useful in the treatment of PTSD.6768 Similarly, β-adrenoceptor antagonists prevent stress-induced impairment of the PFC,69 e.g., propanolol.70
Guanfacine, used as a third-line agent for ADHD after MPH and AMP, is an α2-adrenoceptor agonist. Guanfacine in ADHD Stress deactivates working memory via dopamine Acute stress and dopamine in the PFC

Dopamine shows comparable effects on the PFC as noradrenaline. Acute stress induces very high levels of dopamine in the PFC. Both very high dopamine levels (via D1 receptors) and very low dopamine levels impair PFC function, especially (spatial) working memory.717273 The impairment of working memory by stress can be avoided by D1 antagonists.6

As with D1, moderate D2 receptor stimulation in the PFC strengthens working memory, whereas very strong D2 receptor stimulation in the PFC impairs working memory74 7576

The same effects of dopamine are already known from various COMT gene polymorphisms. COMT controls dopamine degradation in the PFC. Those COMT variants that degrade dopamine more slowly are associated with increased susceptibility to stress- or stimulation-induced impairments in working memory.77 See also COMT gene variant influences stress perception in a sex-specific manner Chronic stress and dopamine in the PFC

Chronic stress decreases dopamine levels in the PFC.78

In contrast, the change in dopamine or norepinephrine levels to acute stress after preceding by 5-week chronic cold stress in rats did not change fundamentally. Prior chronic stress here only slightly reduced the dopamine elevation induced by acute stress, whereas the norepinephrine elevation to acute stress was almost doubled with prior chronic stress.79

1.2.3. Interaction of norepinephrine and dopamine in the stress response

Dopamine and norepinephrine complement each other in mediating stress responses and symptoms
Norepinephrine at intermediate levels via α2A-receptors increases signal strength to all inputs,64 whereas high levels of norepinephrine reduce firing
Dopamine, on the other hand, improves signal quality (reduced noise) by reducing neuronal activation/addressing of non-preferred inputs via D1 receptors.71 However, high D1 receptor stimulation suppresses neuron firing for all directions. As a result, the neuron loses both its spatial orientation and its responsiveness.71

Protein kinase C also impairs the PFC.80 Protein kinase-γ and -ε play a role as stress sensors in the brain.81

This impairment of working memory is a quantitative change in memory functions.

In ADHD, working memory is impaired.

1.2.4. Neurophysiological correlates of acute stress and ADHD Dopamine and norepinephrine receptor antagonists for the treatment of ADHD

Antagonists of D1 or D2 dopamine receptors have rarely been used to treat ADHD
Guanfacine, which is used particularly in ADHD-affected children and adolescents who do not respond to stimulants, acts as an α2-adrenoceptor agonist. Guanfacine thus covers the high-affinity α2-adrenoceptors, so that less norepinephrine is required to activate the PFC-or, after complete coverage of the α2-adrenoceptor, to now deactivate the PFC via the α1- or β-adrenoceptors. As a result, guanfacine acts as an indirect α1- and β-adrenoceptor agonist. ADHD: low DA levels in the PFC.

In ADHD, dopamine levels in the PFC (and striatum) are decreased.
Similarly, methylphenidate and amphetamine medications increase norepinephrine and dopamine levels in the PFC 82 26
Stimulants work the same for ADHD-HI as they do for ADHD-I.

As shown above, the functionality of the PFC is equally impaired when norepinephrine and dopamine levels are too low or too high. Too little norepinephrine or dopamine does not activate the PFC sufficiently to fully initiate working memory.

Thus, the working memory problems in ADHD appear to result from underactivation of the PFC, which can be remedied by appropriately dosed stimulants.

Acute stress is characterized by an increase in dopamine (and norepinephrine) in the PFC.

Chronic stress, on the other hand, can trigger decreased levels of dopamine in the PFC, which likewise impairs working memory.83 Since ADHD is a decades- to lifelong disorder, it is not surprising to find the consequences of chronic stress exposure.

The fact that dopamine levels in the PFC change drastically in chronic stress compared to acute stress corresponds to the changes with respect to cortisol levels in chronic, prolonged stress: whereas cortisol increases in response to stress in acute stress, especially in healthy individuals who are not pre-stressed, chronic stress (depending on the stress phenotype) shows comparatively flattened or exaggerated cortisol stress responses. The basal cortisol level (the cortisol diurnal cycle) is reduced in chronic stress in both stress phenotypes
In this context, it would be conceivable, in purely theoretical terms, that glucocorticoids, which contribute to the increase in dopamine levels in the PFC during stress, are no longer high enough to trigger an increase in dopamine in the PFC, especially in the externalizing stress phenotype (ADHD-HI/ADHD-C), which has a flattened cortisol stress response.

ADHD sufferers who live for several weeks in an extremely low-stimulus environment (alpine hut without Internet) are said to lose their ADHD symptoms, even if this only lasts as long as the low-stimulus environment persists. Even normal everyday life without special stressors restores the ADHD symptoms afterwards.
It would be interesting to learn whether in this condition stimulant administration then worsens the symptomatology. This could indicate that when the stress systems were calmed in an extremely low-stimulus environment, a return to a normal stress response and a normalization of dopamine levels in the PFC would occur.

A report about an alpine hut event for children with ADHD is not very positive.84

1.3. Learning behavior: automatic reactions instead of controlled conclusions

Stress (e.g., fear) alters mammalian learning behavior such that hippocampus-driven learning is replaced by striatum-driven stimulus-response learning.8586
This change in the memory networks involved is a qualitative change in memory functions.

Stress causes other qualitative changes, e.g., in visual memory.85

Stress reduces levels of BDNF and other neurotrophic factors. These are necessary for the brain’s neuroplasticity, i.e. the formation of new synapses, especially in the hippocampus - called “memory formation” or “learning.

ADHD is characterized by learning problems and correlates with decreased levels of BDNF and other neurotrophic factors. ADHD medications normalize the levels of neurotrophic factors.

1.4. Impulsivity due to loss of control

The PFC is a controller over impulsive and emotionally driven behavior. Stress reduces this control of the PFC and thus increases impulsivity.
Impulsivity is one of the central symptoms of ADHD.87

1.5. Addiction due to loss of control

The PFC is a controller over impulsive and emotionally driven behavior. Impaired impulse control by the PFC due to stress correlates, for example, with drug addiction, smoking, alcohol consumption, and overeating88899091

In addition to the PFC, the anterior cingulate cortex (ACC), amygdala, and striatum are involved in addiction symptoms.88

ADHD correlates with significantly increased addiction problems and the brain regions mentioned are all involved in relation to ADHD symptoms.

2. Striatum

The mPFC also appears to control stress responses by regulating the stress response of the mesoaccumbic dopamine system. Rats showed under 240 minutes of restraint stress14

  • Initial
    • A brief increase in norepinephrine in the mPFC
    • A brief increase in dopamine in the nucleus accumbens (a part of the striatum)
  • Then
    • A sustained increase in dopamine in the mPFC
    • A persistent decrease of dopamine in the nucleus accumbens, to below the resting level
  • A selective elimination (depletion) of norepinephrine in the PFC
    • Prevented the increase of noradrenaline in mPFC and
    • Prevented the increase of dopamine in the mPFC and the nucleus accumbens
  • A selective elimination (depletion) of mesocortical dopamine
    • Eliminated the increase of dopamine in the mPFC and
    • Eliminated the reduction of dopamine in the nucleus accumbens
    • Basal catecholamines remained unaffected

Accordingly, the opposing influences of norepinephrine and dopamine in the mPFC determine the stress-induced response of dopamine in the nucleus accumbens.

Repeated alcohol exposure in youth decreased dopamine levels in the nucleus accumbens (striatum) in adult rodents.92 and monkeys.93

In the nucleus accumbens, the dopamine level is also changed by prolonged stress. Depending on whether the stress is controllable or uncontrollable, an increase or decrease in dopamine levels is seen. Controllable stress causes a tonic dopamine increase, while uncontrollable stress causes a tonic dopamine decrease.94959697

The dopamine stress response in the nucleus accumbens appears to be biphasic. A short-term increase in dopamine is followed by a second phase in which dopamine levels depend on control over the stressor.98 Whereas short-term stress is accompanied by a mesolimbic increase in dopamine, long-term stress is characterized by a decrease in dopamine.99

3. Amygdala

During stress, the amygdala increases norepinephrine levels
By means of high levels of norepinephrine, the amygdala moderates anxiety and fear conditioning.100
Whereas conditioned fear is generated by phasically activated neurons, anxiety is generated by permanently activated neurons.101

ADHD correlates significantly with increased anxiety and comorbid anxiety disorders. Further, untreated ADHD significantly increases the risk for later anxiety disorders.

4. Neurophysiological correlates of stress sensitivity and stress resilience

Just as certain states and processes in the brain correlate with stress development and stress symptoms, there are also neurophysiological maps of stress sensitivity and stress resilience.

4.1. Asymmetric activity of the brain hemispheres

A stronger activation of brain regions correlates with a more intense perception of the emotions represented in this brain region. The right brain hemisphere tends to represent negative perceptions and feelings, the left brain hemisphere tends to represent positive ones. People with stronger left than right brain activity perceive positive emotions more intensely, and people with stronger right than left brain activity perceive negative emotions more intensely.102103104 One study was able to reproduce this only for certain methods of analysis. A recent review paper summarizes the state of the art on alpha asymmetry.105106
In humans, one study found lower left anterior and lower right posterior alpha activation in formerly depressed subjects than in never depressed subjects. This pattern resembles that of acutely depressed patients.107
Studies in rhesus monkeys showed that increased right frontal brain activity correlates with anxiety behavior and elevated blood plasma cortisol levels. Monkeys with increased right frontal brain activity have - stable over years - increased CRH levels in the cerebrospinal fluid.108

At the same time, the relative distribution of brain activity between left and right hemispheres is thought to represent a fairly constant personality trait.109 Infants at 10 months of age respond to positive faces with greater activity from left frontal brain regions.110

4.2. Neurotransmitters and stress sensitivity

One study compared mice that showed pronounced stress responses to chronic stress with mice whose responses to chronic stress were indistinguishable from those of unstressed control mice
Stress-resilient mice showed:111

  • Lower norepinephrine levels in the ventral tegmentum than stress-prone mice
  • Unchanged noradrenaline levels in limbic areas, nucleus accumbens and PFC
  • Norepinephrine levels in the ventral tegmentum correlated with social interaction
  • Unchanged excitability of dopaminergic neurons in the ventral tegmentum compared to controls

Stress-prone mice showed:

  • Increased dopaminergic response in the ventral tegmentum
  • Higher dopamine levels in the nucleus accumbens
  • Unchanged dopamine levels in the PFC

This suggests higher dopamine release from the ventral tegmentum, which projects dopaminergically to the nucleus accumbens.

Stress-prone mice showed:

  • A reduced expression of the transcription factor c-fos in the locus coeruleus compared with controls and stress-resistant mice. This was fully explained by noradrenergic neurons projecting to the ventral tegmentum. However, the number of non-NE-activated cells (TH-negative) that projected to the ventral tegmentum and NE-activated cells (TH-positive) that did not project to the ventral tegmentum remained unchanged.
  • The reduced number of activated noradrenergic cells in the locus coeruleus that projected to the ventral tegmentum correlated with reduced social interaction time.

This suggests that both a reduced activation state of noradrenergic cells in the locus coeruleus projecting to the ventral tegmentum and a reduced amount of noradrenaline released into the ventral tegmentum correlate with vulnerability to emotional stress.

4.3. Even a single acute stress increases the sensitivity to stress

Illustration according to Holly, Miczek.112

Even a single (severe) acute stress can cause long-lasting neuroplastic changes in dopaminergic cells of the ventral tegmentum (VTA) (similar to what drug abuse does) 113114 115

VTA dopamine neurons are relatively depolarized in the ground state (baseline) and thus typically at or very close to the action potential threshold.113

  • Acute stress causes at dopamine neurons in the VTA113114
    • Induced long-term potentiation at glutamatergic (= exitatory) synapses
      • Incorporation of new AMPA receptors116
      • Thereby increasing AMPA to NMDA ratio113115 116
        • Where:
          • Only in medial VTA dopamine neurons projecting to the mPFC (venom as a stressor)117
          • Not in VTA dopamine neurons projecting to the NAc sheath (venom as a stressor)117
        • How long:
          • Occurs within 2 h after stress118
          • Persists for at least 24 h118
        • Consequences:
          • Increases calcium permeability and changes calcium dynamics
            • Thus subliminal stimulation can induce robust long-term potentiation119
            • Thereby increasing the future excitability of the postsynaptic nerve cell116
      • AMPA and NMDA receptors in the VTA mediate increased dopamine output in the mPFC to acute pain stress120
        • Blockade of AMPA and NMDA receptors in the VTA suppresses dopamine release in the mPFC in response to acute pain stress120
        • Blockade of glucocorticoid receptors in the mPFC disrupts the signaling circuit that mediates (on acute pain stress) the increased glutamate level in the VTA and the increased dopamine level in the mPFC.120
    • Blocked long-term potentiation at GABAergic (= inhibitory) synapses113114

This loss of long-term potentiation at inhibitory synapses on VTA dopamine neurons could remove the brake on the system and, in combination with the induced long-term potentiation at excitatory (glutamatergic) synapses, increase the responsiveness of VTA dopamine neurons to future stress or reward stimuli.112

5. Dopamine and stress

More about this in detail under Dopamine and stress In the section Dopamine in the chapter Neurological aspects.

  1. Chrousos, Gold (1992): The concepts of stress and stress system disorders. Overview of physical and behavioral homeostasis. JAMA. 1992 Mar 4;267(9):1244-52., zitiert nach Pacák, Palkovits (2001): Stressor Specificity of Central Neuroendocrine Responses: Implications for Stress-Related Disorders; Endocrine Reviews, Volume 22, Issue 4, 1 August 2001, Pages 502–548,

  2. Arnsten (2009): Stress signalling pathways that impair prefrontal cortex structure and function. Nat Rev Neurosci. 2009 Jun;10(6):410-22. doi: 10.1038/nrn2648.

  3. Rodrigues, Leão, Carvalho, Almeida, Sousa (2010): Potential programming of dopaminergic circuits by early life stress. Psychopharmacology (Berl). 2011 Mar;214(1):107-20. doi: 10.1007/s00213-010-2085-3.

  4. Liston, Miller, Goldwater, Radley, Rocher, Hof, Morrison, McEwen (2006): Stress-induced alterations in prefrontal cortical dendritic morphology predict selective impairments in perceptual attentional set-shifting. J Neurosci. 2006 Jul 26;26(30):7870-4.

  5. Mohammadian, Sahraei, Meftahi, Ali‐Beik (2017): Effects of unilatral‐ and bilateral inhibition of rostral ventral tegmental area and central nucleus of amygdala on morphine‐induced place conditioning in male Wistar rat. Clin Exp Pharmacol Physiol. 2017; 44: 403– 412.

  6. Murphy, Arnsten, Goldman-Rakic, Roth (1996): Increased dopamine turnover in the prefrontal cortex impairs spatial working memory performance in rats and monkeys. Proc Natl Acad Sci U S A. 1996 Feb 6;93(3):1325-9.

  7. Arnsten, Goldman-Rakic (1998): Noise stress impairs prefrontal cortical cognitive function in monkeys: evidence for a hyperdopaminergic mechanism. Arch Gen Psychiatry. 1998 Apr;55(4):362-8.

  8. Bahari, Meftahi, Meftahi (2018): Dopamine effects on stress-induced working memory deficits. Behav Pharmacol. 2018 Oct;29(7):584-591. doi: 10.1097/FBP.0000000000000429.

  9. Zahrt, Taylor, Mathew, Arnsten (1997): Supranormal Stimulation of D1 Dopamine Receptors in the Rodent Prefrontal Cortex Impairs Spatial Working Memory Performance. Journal of Neuroscience 1 November 1997, 17 (21) 8528-8535; DOI:

  10. Taylor, Birnbaum, Ubriani, Arnsten (1999): Activation of cAMP-dependent protein kinase A in prefrontal cortex impairs working memory performance. J Neurosci. 1999 Sep 15;19(18):RC23.

  11. Nomura, Bouhadana, Morel, Faure, Cauli, Lambolez, Hepp (2014): Noradrenalin and dopamine receptors both control cAMP-PKA signaling throughout the cerebral cortex. Front Cell Neurosci. 2014 Aug 21;8:247. doi: 10.3389/fncel.2014.00247. eCollection 2014.

  12. Gamo, Lur, Higley, Wang, Paspalas, Vijayraghavan, Yang, Ramos, Peng, Kata, Boven, Lin, Roman, Lee, Arnsten (2015): Stress Impairs Prefrontal Cortical Function via D1 Dopamine Receptor Interactions With Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels, Biological Psychiatry, Volume 78, Issue 12, 2015, Pages 860-870, ISSN 0006-3223,

  13. Ferenczi, Zalocusky, Liston, Grosenick, Warden, Amatya, Katovich, Mehta, Patenaude, Ramakrishnan, Kalanithi, Etkin, Knutson, Glover, Deisseroth (2016): Prefrontal cortical regulation of brainwide circuit dynamics and reward-related behavior. Science. 2016 Jan 1;351(6268):aac9698. doi: 10.1126/science.aac9698

  14. Pascucci, Ventura, Latagliata, Cabib, Puglisi-Allegra (2007): The medial prefrontal cortex determines the accumbens dopamine response to stress through the opposing influences of norepinephrine and dopamine. Cereb Cortex. 2007 Dec;17(12):2796-804.

  15. 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

  16. Ehteram, Sahraei, Meftahi, Khosravi (2017): Effect of Intermittent Feeding on Gonadal Function in Male And Female NMRI Mice During Chronic Stress. Brazilian Archives of Biology and Technology, 60, e17160607.

  17. Butts, Weinberg, Young, Phillips (2011): Glucocorticoid receptors in the prefrontal cortex regulate stress-evoked dopamine efflux and aspects of executive function. Proceedings of the National Academy of Sciences Nov 2011, 108 (45) 18459-18464; DOI: 10.1073/pnas.1111746108

  18. Shansky, Lipps (2013): Stress-induced cognitive dysfunction: hormone-neurotransmitter interactions in the prefrontal cortex. Front. Hum. Neurosci. 7:123. doi: 10.3389/fnhum.2013.00123

  19. Lupien, Gillin, Hauger (1999): Working memory is more sensitive than declarative memory to the acute effects of corticosteroids: a dose-response study in humans. Behav Neurosci. 1999 Jun;113(3):420-30.

  20. Gründemann, Köster, Kiefer, Breidert, Engelhardt, Spitzenberger, Obermüller, Schömig (1998): Transport of Monoamine Transmitters by the Organic Cation Transporter Type 2, OCT2. J. Biol. Chem. 1998 273: 30915-. doi:10.1074/jbc.273.47.30915

  21. Gründemann, Schechinger, Rappold, Schömig (1998): Molecular identification of the corticosterone-sensitive extraneuronal catecholamine transporter. Nature Neuroscience volume 1, pages349–351, 1998

  22. Mizoguchi, Yuzurihara, Ishige, Sasaki, Chui, Tabira (2000): Chronic stress induces impairment of spatial working memory because of prefrontal dopaminergic dysfunction. J Neurosci. 2000;20(4):1568–1574. doi:10.1523/JNEUROSCI.20-04-01568.2000

  23. Mizoguchi, Shoji, Ikeda, Tanaka, Tabira (2008): Persistent depressive state after chronic stress in rats is accompanied by HPA axis dysregulation and reduced prefrontal dopaminergic neurotransmission. Pharmacol Biochem Behav. 2008;91(1):170–175. doi:10.1016/j.pbb.2008.07.002

  24. Tielbeek, Al-Itejawi, Zijlmans, Polderman, Buckholtz, Popma (2018): The impact of chronic stress during adolescence on the development of aggressive behavior: A systematic review on the role of the dopaminergic system in rodents. Neurosci Biobehav Rev. 2018 Aug;91:187-197. doi: 10.1016/j.neubiorev.2016.10.009.

  25. Miner, Jedema, Moore, Blakely, Grace, Sesack (2006): Chronic stress increases the plasmalemmal distribution of the norepinephrine transporter and the coexpression of tyrosine hydroxylase in norepinephrine axons in the prefrontal cortex. J Neurosci. 2006 Feb 1;26(5):1571-8.

  26. Bymaster FP, Katner JS, Nelson DL, et al. Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: a potential mechanism for efficacy in attention deficit/hyperactivity disorder. Neuropsychopharmacology. 2002;27:699–711.

  27. Boksa, El-Khodor (2003): Birth insult interacts with stress at adulthood to alter dopaminergic function in animal models: possible implications for schizophrenia and other disorders, Neuroscience & Biobehavioral Reviews, Volume 27, Issues 1–2, 2003, Pages 91-101, ISSN 0149-7634,

  28. Brake, Noel, Boksa, Gratton (1997): Influence of perinatal factors on the nucleus accumbens dopamine response to repeated stress during adulthood: an electrochemical study in the rat, Neuroscience, Volume 77, Issue 4, 1997, Pages 1067-1076, ISSN 0306-4522,

  29. Wayne G. Brake, Ron M. Sullivan and Alain 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; DOI:

  30. Fride, Weinstock (1988): Prenatal stress increase anxiety related behavior and alters cerebral lateralization of dopamine activity, Life Sciences, Volume 42, Issue 10, 1988, Pages 1059-1065, ISSN 0024-3205,

  31. Kippin, Szumlinski, Kapasova, Rezner, See (2008): Prenatal stress enhances responsiveness to cocaine. Neuropsychopharmacology. 2008 Mar;33(4):769-82.

  32. Weber, Graack, Scholl, Renner, Forster, Watt (2018): Enhanced dopamine D2 autoreceptor function in the adult prefrontal cortex contributes to dopamine hypoactivity following adolescent social stress. Eur J Neurosci. 2018 Jul;48(2):1833-1850. doi: 10.1111/ejn.14019.

  33. Novick, Forster, Hassell, Davies, Scholl, Renner, Watt (2015): Increased dopamine transporter function as a mechanism for dopamine hypoactivity in the adult infralimbic medial prefrontal cortex following adolescent social stress. Neuropharmacology. 2015 Oct;97:194-200. doi: 10.1016/j.neuropharm.2015.05.032.

  34. Wright, Hébert, Perrot-Sinal (2008): Periadolescent stress exposure exerts long-term effects on adult stress responding and expression of prefrontal dopamine receptors in male and female rats. Psychoneuroendocrinology. 2008 Feb;33(2):130-42.

  35. Han, Li, Xue, Shao, Wang (2012): Early social isolation disrupts latent inhibition and increases dopamine D2 receptor expression in the medial prefrontal cortex and nucleus accumbens of adult rats. Brain Res. 2012 Apr 4;1447:38-43. doi: 10.1016/j.brainres.2012.01.058.

  36. Watt, Burke, Renner, Forster (2009): Adolescent male rats exposed to social defeat exhibit altered anxiety behavior and limbic monoamines as adults. Behav Neurosci. 2009 Jun;123(3):564-76. doi: 10.1037/a0015752.

  37. Watt, Roberts, Scholl, Meyer, Miiller, Barr, Novick, Renner, Forster (2014): Decreased prefrontal cortex dopamine activity following adolescent social defeat in male rats: role of dopamine D2 receptors. Psychopharmacology (Berl). 2014 Apr;231(8):1627-36. doi: 10.1007/s00213-013-3353-9.

  38. Bagalkot, Jin, Prabhu, Muna, Cui, Yadav, Chae, Chung (2015): Chronic social defeat stress increases dopamine D2 receptor dimerization in the prefrontal cortex of adult mice. Neuroscience. 2015;311:444–452. doi:10.1016/j.neuroscience.2015.10.024

  39. Enman, Arthur, Ward, Perrine, Unterwald (2015): Anhedonia, Reduced Cocaine Reward, and Dopamine Dysfunction in a Rat Model of Posttraumatic Stress Disorder. Biol Psychiatry. 2015 Dec 15;78(12):871-9. doi: 10.1016/j.biopsych.2015.04.024.

  40. Lin, Tung, Liu (2016): Escitalopram reversed the traumatic stress-induced depressed and anxiety-like symptoms but not the deficits of fear memory. Psychopharmacology (Berl). 2016 Apr;233(7):1135-46. doi: 10.1007/s00213-015-4194-5.

  41. Sugama, Sekiyama, Kodama, Takamatsu, Takenouchi, Hashimoto, Bruno, Kakinuma (2016): Chronic restraint stress triggers dopaminergic and noradrenergic neurodegeneration: Possible role of chronic stress in the onset of Parkinson’s disease. Brain Behav Immun. 2016 Jan;51:39-46. doi: 10.1016/j.bbi.2015.08.015.

  42. George, Knox, Curtis, Aldridge, Valentino, Liberzon (2013): Altered locus coeruleus-norepinephrine function following single prolonged stress. Eur J Neurosci. 2013 Mar;37(6):901-9. doi: 10.1111/ejn.12095.

  43. Rusnák, Kvetnanský, Jeloková, Palkovits (2001): Effect of novel stressors on gene expression of tyrosine hydroxylase and monoamine transporters in brainstem noradrenergic neurons of long-term repeatedly immobilized rats. Brain Res. 2001 Apr 27;899(1-2):20-35.

  44. Zhao, Shin, Park, Kim, Lee, Cho, Lee (2016): Effects of (-)-sesamin on chronic stress-induced memory deficits in mice. Neurosci Lett. 2016 Nov 10;634:114-118. doi: 10.1016/j.neulet.2016.09.055.

  45. Cho, Deisseroth, Bolshakov (2013): Synaptic Encoding of Fear Extinction in mPFC-amygdala Circuits, Neuron, Volume 80, Issue 6, 2013, Pages 1491-1507, ISSN 0896-6273,

  46. Parker, Buckmaster, Justus, Schatzberg, Lyons (2005): Mild early life stress enhances prefrontal-dependent response inhibition in monkeys. Biol Psychiatry. 2005 Apr 15;57(8):848-55.

  47. Meaney, Diorio, Francis, Widdowson, LaPlante, Caldji, Sharma, Seckl, Plotsky (1996): Early environmental regulation of forebrain glucocorticoid receptor gene expression: implications for adrenocortical responses to stress. Dev Neurosci. 1996;18(1-2):49-72.

  48. Patel PD1, Katz M, Karssen AM, Lyons (2008): Stress-induced changes in corticosteroid receptor expression in primate hippocampus and prefrontal cortex. Psychoneuroendocrinology. 2008 Apr;33(3):360-7. doi: 10.1016/j.psyneuen.2007.12.003.

  49. Lehner, Karas-Ruszczyk, Zakrzewska, Gryz, Wislowska-Stanek, Kolosowska, Chmielewska, Skorzewska, Turzynska, Sobolewska, Mierzejewski, Plaznik (2018): Chronic stress changes prepulse inhibition after amphetamine challenge: the role of the dopaminergic system. J Physiol Pharmacol. 2018 Jun;69(3). doi: 10.26402/jpp.2018.3.15.

  50. Buschman, Miller (2007): Top-down versus bottom-up control of attention in the prefrontal and posterior parietal cortices. Science. 2007 Mar 30;315(5820):1860-2.

  51. Liston, McEwen, Casey (2009): Psychosocial stress reversibly disrupts prefrontal processing and attentional control. Proc Natl Acad Sci U S A. 2009 Jan 20;106(3):912-7. doi: 10.1073/pnas.0807041106.

  52. Birrell, Brown (2000): Medial frontal cortex mediates perceptual attentional set shifting in the rat. J Neurosci. 2000 Jun 1;20(11):4320-4.

  53. Liston, Miller, Goldwater, Radley, Rocher, Hof, Morrison, McEwen (2006): Stress-induced alterations in prefrontal cortical dendritic morphology predict selective impairments in perceptual attentional set-shifting. J Neurosci. 2006 Jul 26;26(30):7870-4.

  54. Luethi, Meier, Sandi (2008): Stress effects on working memory, explicit memory, and implicit memory for neutral and emotional stimuli in healthy men. Front Behav Neurosci. 2009 Jan 15;2:5. doi: 10.3389/neuro.08.005.2008. eCollection 2008.

  55. Qin, Hermans, van Marle, Luo, Fernández (2009): Acute psychological stress reduces working memory-related activity in the dorsolateral prefrontal cortex. Biol Psychiatry. 2009 Jul 1;66(1):25-32. doi: 10.1016/j.biopsych.2009.03.006.

  56. Funahashi, Bruce, Goldman-Rakic (1989): Mnemonic coding of visual space in the monkey’s dorsolateral prefrontal cortex. J Neurophysiol. 1989 Feb;61(2):331-49.

  57. Funahashi, Bruce, Goldman-Rakic (1993): Dorsolateral prefrontal lesions and oculomotor delayed-response performance: evidence for mnemonic “scotomas”. J Neurosci. 1993 Apr;13(4):1479-97.

  58. Arnsten (2000): Through the looking glass: differential noradenergic modulation of prefrontal cortical function. Neural Plast. 2000;7(1-2):133-46.

  59. Arnsten, Goldman-Rakic (1985): Alpha 2-adrenergic mechanisms in prefrontal cortex associated with cognitive decline in aged nonhuman primates. Science. 1985 Dec 13;230(4731):1273-6.

  60. Birnbaum, Gobeske, Auerbach, Taylor, Arnsten (1999): A role for norepinephrine in stress-induced cognitive deficits: alpha-1-adrenoceptor mediation in the prefrontal cortex. Biol Psychiatry. 1999 Nov 1;46(9):1266-74.

  61. Ramos, Colgan, Nou, Ovadia, Wilson, Arnsten (2005): The beta-1 adrenergic antagonist, betaxolol, improves working memory performance in rats and monkeys. Biol Psychiatry. 2005 Dec 1;58(11):894-900.

  62. Ramos, Stark, Verduzco, van Dyck, Arnsten (2006): Alpha2A-adrenoceptor stimulation improves prefrontal cortical regulation of behavior through inhibition of cAMP signaling in aging animals. Learn Mem. 2006 Nov-Dec;13(6):770-6.

  63. Li, Mao, Wang, Mei (1999): Alpha-2 adrenergic modulation of prefrontal cortical neuronal activity related to spatial working memory in monkeys. Neuropsychopharmacology. 1999 Nov;21(5):601-10.

  64. Wang, Ramos, Paspalas, Shu, Simen, Duque, Vijayraghavan, Brennan, Dudley, Nou, Mazer, McCormick, Arnsten (2007): Alpha2A-adrenoceptors strengthen working memory networks by inhibiting cAMP-HCN channel signaling in prefrontal cortex. Cell. 2007 Apr 20;129(2):397-410.

  65. Arnsten, Mathew, Ubriani, Taylor, Li (1999): Alpha-1 noradrenergic receptor stimulation impairs prefrontal cortical cognitive function. Biol Psychiatry. 1999 Jan 1;45(1):26-31.

  66. Birnbaum, Gobeske, Auerbach, Taylor, Arnsten (1999): A role for norepinephrine in stress-induced cognitive deficits: alpha-1-adrenoceptor mediation in the prefrontal cortex. Biol Psychiatry. 1999 Nov 1;46(9):1266-74.

  67. Taylor, Raskind (2002): The alpha1-adrenergic antagonist prazosin improves sleep and nightmares in civilian trauma posttraumatic stress disorder. J Clin Psychopharmacol. 2002 Feb;22(1):82-5.

  68. Raskind, Peskind, Kanter, Petrie, Radant, Thompson, Dobie, Hoff, Rein, Straits-Tröster, Thomas, McFall (2003): Reduction of nightmares and other PTSD symptoms in combat veterans by prazosin: a placebo-controlled study. Am J Psychiatry. 2003 Feb;160(2):371-3.

  69. Alexander, Hillier, Smith, Tivarus, Beversdorf (2007): Beta-adrenergic modulation of cognitive flexibility during stress. J Cogn Neurosci. 2007 Mar;19(3):468-78.

  70. Alexander, Hillier, Smith, Tivarus, Beversdorf (2007): Beta-adrenergic modulation of cognitive flexibility during stress. J Cogn Neurosci. 2007 Mar;19(3):468-78.

  71. 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.

  72. Sawaguchi, Goldman-Rakic (1991): D1 dopamine receptors in prefrontal cortex: involvement in working memory. Science. 1991 Feb 22;251(4996):947-50.

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

  74. Kimberg, D’Esposito, Farah (1997): Effects of bromocriptine on human subjects depend on working memory capacity. Neuroreport. 1997 Nov 10;8(16):3581-5.

  75. Druzin, Kurzina, Malinina, Kozlov (2000): The effects of local application of D2 selective dopaminergic drugs into the medial prefrontal cortex of rats in a delayed spatial choice task. Behav Brain Res. 2000 Apr;109(1):99-111.

  76. Gibbs, D’Esposito (2005): A functional MRI study of the effects of bromocriptine, a dopamine receptor agonist, on component processes of working memory. Psychopharmacology (Berl). 2005 Aug;180(4):644-53.

  77. Egan, Goldberg, Kolachana, Callicott, Mazzanti, Straub, Goldman, Weinberger (20019): Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia. Proc Natl Acad Sci U S A. 2001 Jun 5;98(12):6917-22.

  78. Gresch, Sved, Zigmond, Finlay (1994): Stress-induced sensitization of dopamine and norepinephrine efflux in medial prefrontal cortex of the rat. J Neurochem. 1994 Aug;63(2):575-83.

  79. Finlay, Zigmond, Abercrombie (1995): Increased dopamine and norepinephrine release in medial prefrontal cortex induced by acute and chronic stress: effects of diazepam. Neuroscience 64, 619–628.

  80. Birnbaum, Yuan, Wang, Vijayraghavan, Bloom, Davis, Gobeske, Sweatt, Manji, Arnsten (2004): Protein kinase C overactivity impairs prefrontal cortical regulation of working memory. Science. 2004 Oct 29;306(5697):882-4.

  81. Barnett, Madgwick, Takemoto (2007): Protein kinase C as a stress sensor. Cell Signal. 2007 Sep;19(9):1820-9.

  82. Steinhausen, Rothenberger, Döpfner (2010): Handbuch ADHS, Seite 84, 85

  83. Mizoguchi, Yuzurihara, Ishige, Sasaki, Chui, Tabira (2000): Chronic stress induces impairment of spatial working memory because of prefrontal dopaminergic dysfunction. J Neurosci. 2000 Feb 15;20(4):1568-74.

  84. Erfahrungsbericht einer Mutter zum Almprojekt der Sinnstiftung bei ADHS-Deutschland e.V., aufgerufen am 12.01.2020

  85. Vogel, Klumpers, Schröder, Oplaat, Krugers, Oitzl, Joëls, Doeller, Fernández (2017): Stress Induces a Shift Towards Striatum-Dependent Stimulus-Response Learning via the Mineralocorticoid Receptor. Neuropsychopharmacology. 2017 May;42(6):1262-1271. doi: 10.1038/npp.2016.262.

  86. Gasbarri, Pompili, Packard, Tomaz (2014) Habit learning and memory in mammals: behavioral and neural characteristics. Neurobiol Learn Mem. 2014 Oct;114:198-208. doi: 10.1016/j.nlm.2014.06.010.

  87. Epstein, Erkanli, Conners, Klaric, Costello, Angold (2003): Relations between Continuous Performance Test performance measures and ADHD behaviors. J Abnorm Child Psychol. 2003 Oct;31(5):543-54.

  88. Li, Sinha (2008): Inhibitory control and emotional stress regulation: neuroimaging evidence for frontal-limbic dysfunction in psycho-stimulant addiction. Neurosci Biobehav Rev. 2008;32(3):581-97. doi: 10.1016/j.neubiorev.2007.10.003.

  89. Acton (2003): Measurement of impulsivity in a hierarchical model of personality traits: implications for substance use. Subst Use Misuse. 2003 Jan;38(1):67-83.

  90. Dawe, Loxton (2004): The role of impulsivity in the development of substance use and eating disorders. Neurosci Biobehav Rev. 2004 May;28(3):343-51.

  91. Butler, Montgomery (2004): Impulsivity, risk taking and recreational ‘ecstasy’ (MDMA) use. Drug Alcohol Depend. 2004 Oct 5;76(1):55-62.

  92. Karkhanis, Rose, Huggins, Konstantopoulos, Jones (2015): Chronic intermittent ethanol exposure reduces presynaptic dopamine neurotransmission in the mouse nucleus accumbens. Drug Alcohol Depend. 2015 May 1;150:24-30. doi: 10.1016/j.drugalcdep.2015.01.019.

  93. Siciliano, Calipari, Yorgason, Lovinger, Mateo, Jimenez, Helms, Grant, Jones (2016): Increased presynaptic regulation of dopamine neurotransmission in the nucleus accumbens core following chronic ethanol self-administration in female macaques. Psychopharmacology (Berl). 2016 Apr;233(8):1435-43. doi: 10.1007/s00213-016-4239-4.

  94. Lloyd, Dayan (2016): Safety out of control: dopamine and defence. Behav Brain Funct. 2016 May 23;12(1):15. doi: 10.1186/s12993-016-0099-7.

  95. Cabib, Puglisi-Allegra (2012): The mesoaccumbens dopamine in coping with stress. Neurosci Biobehav Rev. 2012 Jan;36(1):79-89. doi: 10.1016/j.neubiorev.2011.04.012.

  96. Cabib, Puglisi-Allegra (1994): Opposite responses of mesolimbic dopamine system to controllable and uncontrollable aversive experiences. J Neurosci. 1994 May;14(5 Pt 2):3333-40.

  97. Cabib, Puglisi-Allegra (1996): Stress, depression and the mesolimbic dopamine system. Psychopharmacology (Berl). 1996 Dec;128(4):331-42.

  98. Puglisi-Allegra, Imperato, Angelucci, Cabib (1991): Acute stress induces time-dependent responses in dopamine mesolimbic system. Brain Res. 1991 Jul 19;554(1-2):217-22.

  99. Imperato, Cabib, Puglisi-Allegra (1993): Repeated stressful experiences differently affect the time-dependent responses of the mesolimbic dopamine system to the stressor. Brain Res. 1993 Jan 22;601(1-2):333-6.

  100. Debiec, LeDoux (2006) Noradrenergic signaling in the amygdala contributes to the reconsolidation of fear memory: treatment implications for PTSD. Ann N Y Acad Sci. 2006 Jul;1071:521-4.

  101. Sah (2017): Fear, Anxiety, and the Amygdala. Neuron. 2017 Sep 27;96(1):1-2. doi: 10.1016/j.neuron.2017.09.013.

  102. Wheeler, Davidson, Tomarken (1993): Frontal brain asymmetry and emotional reactivity: a biological substrate of affective style. Psychophysiology. 1993 Jan;30(1):82-9. doi: 10.1111/j.1469-8986.1993.tb03207.x. PMID: 8416065.

  103. Hannesdóttir, Doxie, Bell, Ollendick, Wolfe (2010): A longitudinal study of emotion regulation and anxiety in middle childhood: Associations with frontal EEG asymmetry in early childhood. Dev Psychobiol. 2010 Mar;52(2):197-204. doi: 10.1002/dev.20425. PMID: 20112261.

  104. Kim, Bell (2006): Frontal EEG asymmetry and regulation during childhood. Ann N Y Acad Sci. 2006 Dec;1094:308-12. doi: 10.1196/annals.1376.040. PMID: 17347367.

  105. Hagemann, Naumann, Becker, Maier, Bartussek (2003): Frontal brain asymmetry and affective style: a conceptual replication. Psychophysiology. 1998 Jul;35(4):372-88. PMID: 9643052.

  106. Allen, Keune, Schönenberg, Nusslock (2018): Frontal EEG alpha asymmetry and emotion: From neural underpinnings and methodological considerations to psychopathology and social cognition. Psychophysiology. 2018 Jan;55(1). doi: 10.1111/psyp.13028. PMID: 29243266.

  107. Henriques, Davidson (1990): Regional brain electrical asymmetries discriminate between previously depressed and healthy control subjects. J Abnorm Psychol. 1990 Feb;99(1):22-31. doi: 10.1037//0021-843x.99.1.22. PMID: 2307762.

  108. Kalin, Shelton, Davidson (2000): Cerebrospinal fluid corticotropin-releasing hormone levels are elevated in monkeys with patterns of brain activity associated with fearful temperament. Biol Psychiatry. 2000 Apr 1;47(7):579-85. doi: 10.1016/s0006-3223(99)00256-5. PMID: 10745049.

  109. Grawe (2004): Neuropsychotherapie, Seite 130

  110. Davidson, Fox (1982): Asymmetrical brain activity discriminates between positive and negative affective stimuli in human infants. Science. 1982 Dec 17;218(4578):1235-7. doi: 10.1126/science.7146906. PMID: 7146906.

  111. Isingrini, Perret, Rainer, Amilhon, Guma, Tanti, Martin, Robinson, Moquin, Marti, Mechawar, Williams, Gratton, Giros (2016): Resilience to chronic stress is mediated by noradrenergic regulation of dopamine neurons. Nat Neurosci. 2016 Apr;19(4):560-3. doi: 10.1038/nn.4245.

  112. Holly, Miczek (2016): Ventral tegmental area dopamine revisited: effects of acute and repeated stress. Psychopharmacology (Berl). 2016 Jan;233(2):163-86. doi: 10.1007/s00213-015-4151-3. PMID: 26676983; PMCID: PMC4703498. REVIEW

  113. Graziane, Polter, Briand, Pierce, Kauer (2013): Kappa opioid receptors regulate stress-induced cocaine seeking and synaptic plasticity. Neuron. 2013 Mar 6;77(5):942-54. doi: 10.1016/j.neuron.2012.12.034. PMID: 23473323; PMCID: PMC3632376.

  114. Niehaus, Murali, Kauer (2010): Drugs of abuse and stress impair LTP at inhibitory synapses in the ventral tegmental area. Eur J Neurosci. 2010 Jul;32(1):108-17. doi: 10.1111/j.1460-9568.2010.07256.x. PMID: 20608969; PMCID: PMC2908505.

  115. Dong, Saal, Thomas, Faust, Bonci, Robinson, Malenka (2004): Cocaine-induced potentiation of synaptic strength in dopamine neurons: behavioral correlates in GluRA(-/-) mice. Proc Natl Acad Sci U S A. 2004 Sep 28;101(39):14282-7. doi: 10.1073/pnas.0401553101. PMID: 15375209; PMCID: PMC521147.

  116. Malinow, Malenka (2002): AMPA receptor trafficking and synaptic plasticity. Annu Rev Neurosci. 2002;25:103-26. doi: 10.1146/annurev.neuro.25.112701.142758. PMID: 12052905. REVIEW

  117. Lammel, Ion, Roeper, Malenka (2011): Projection-specific modulation of dopamine neuron synapses by aversive and rewarding stimuli. Neuron. 2011 Jun 9;70(5):855-62. doi: 10.1016/j.neuron.2011.03.025. PMID: 21658580; PMCID: PMC3112473.

  118. Daftary, Panksepp, Dong, Saal (2009): Stress-induced, glucocorticoid-dependent strengthening of glutamatergic synaptic transmission in midbrain dopamine neurons. Neurosci Lett. 2009 Mar 20;452(3):273-6. doi: 10.1016/j.neulet.2009.01.070. PMID: 19348737; PMCID: PMC2667622.

  119. Polter, Kauer (2014): Stress and VTA synapses: implications for addiction and depression. Eur J Neurosci. 2014 Apr;39(7):1179-88. doi: 10.1111/ejn.12490. PMID: 24712997; PMCID: PMC4019343. REVIEW

  120. Butts, Phillips (2013): Glucocorticoid receptors in the prefrontal cortex regulate dopamine efflux to stress via descending glutamatergic feedback to the ventral tegmental area. Int J Neuropsychopharmacol. 2013 Sep;16(8):1799-807. doi: 10.1017/S1461145713000187. PMID: 23590841.

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