6. Dopamine action: DA receptors
Dopamine receptors are predominantly (and in vertebrates are exclusively) coupled to G-proteins. They are orders of magnitude slower than ionotropic receptors.1
Activation of dopamine receptors causes changes in intracellular cAMP levels and triggers gene transcription via a signaling cascade. There are 2 classes of dopamine receptors, differentiated by G-protein partners and intracellular signaling mechanisms:2
The D1-like receptors (D1 and D5) are Gs/olf-coupled. Their activation increases intracellular cAMP and has an excitatory effect.
The D2-like receptors (D2, D3 and D4) are Gi/o coupled. Their activation reduces intracellular cAMP and has an inhibitory effect.
The D1-like dopamine receptors (D1 and D5) are activated postsynaptically by dopamine released from the presynaptic neuron into the synaptic cleft. When activated, they enhance neuronal activity. This is a phasic response.
The D2-like dopamine receptors are partly postsynaptic but can also be presynaptic. Presynaptic dopamine receptors are activated by extracellular dopamine exiting the synapse. This action serves as an inhibitory feedback mechanism when dopamine levels exceed reuptake capacity.3 Postsynaptically, D2-like receptors have an inhibitory effect on neuronal activity.
Rats with low dopamine receptor density in the striatum, thus with lower dopaminergic binding capacity, are more susceptible to rewarding/reinforcing substances.4
In addition to signal transduction via the adenylyl cyclase-cAMP system (the main mechanism of action), dopamine receptors also activate phospho-lipase C via the Gq/11 system and increase intracellular calcium levels. Dopamine receptors besides interact with glutamate receptors and mobilize intracellular Ca2+ stores.5
Dopamine receptors can occur as monomers, as dimeric and/or as oligomeric complexes. This can occur by association of different subtypes, either alone or with other GPCRs and ligand-gated channels. As homodimers occur:
- D1R-D2R
- D2R-D4R
- D1R-D3R
- D2R-D3R
- D2R-D5R
Dimer/oligomeric complexes exhibit pharmacological and functional properties that differ from those of the receptors that form them. Oligomeric complexes with dopamine receptors may be associated with adenosine A1 and A2, serotonergic 5-HT2A, histaminergic H3, glutamatergic mGlu5, and NMDA receptors.6
- 6.1. Frequency distribution of dopamine receptors
- 6.2. Dopamine affinity of dopamine receptors
- 6.3. Dopamine receptors mostly extrasynaptic
- 6.4. D1-like dopamine receptors: activating
- 6.5. D2-like dopamine receptors: inhibitory
- 6.6. Heteromeric
- 6.7. G protein-independent dopamine receptor activation
- 6.8. Dopamine agonists and antagonists
6.1. Frequency distribution of dopamine receptors
The distribution of receptors (in the rat) is (from frequent to rare):
- D1 (approx. 3 to 5 times as frequent as D2)
- D2
- D3 (D3 to D5 are considerably less frequent than D1 and D2)
- D5
- D4
Within brain regions, the frequency of dopamine receptors differs:7
PFC:
- Frequent
- D1
- D4
- Rare
- D2
- D3
- D5
Striatum:
- D1 (dorsal and ventral)
- D2 (dorsal and ventral)
- D3 (ventral) (dorsal?)
- Hardly D4
- Hardly D5
- D1 and D2 are found separately on D1 and D2 MSNs, respectively
- D1-MSN
- predominantly express D2
- approx. 50 %
- direct way
- projects GABAerg from striatum into inner pallidum and substantia nigra pars reticulata
- from inner pallidum and substantia nigra pars reticulata further GABAerg into thalamus
- Result: Increase in thalamic activity (disinhibition: two inhibitory neurons connected in series).
- enables movement and reinforcement learning
- D2-MSN
- predominantly express D2
- approx. 50 %
- indirect way
- projects GABAerg from striatum into outer pallidum
- from outer pallidum further GABAerg into nucleus subthalamicus
- from nucleus subthalamicus further glutamatergic to the GABAergic neurons of the inner pallidum and the pars reticulata of the nucleus niger
- inhibits, inhibits movement and reinforcement learning
- Both MSN types
- respond to dopamine release from non-synaptic varicosities
- can receive synapse-like inputs of dopamine axons with connections between dopamine varicosities and GABAergic postsynaptic assemblies
- D1-MSN
- D2 are also expressed on dopamine axons
Nucleus accumbens:
- D3 frequent
- D1
- D2
Nucleus caudatus:
- D1
- D2
Putamen ventral:
- D3 moderate
Blockade of dopamine receptors increases the release of acetylcholine. Acetylcholine is partly responsible for the development of extrapyramidal symptoms.8
6.2. Dopamine affinity of dopamine receptors
Dopamine has different affinities for different receptors and within them depending on the gene variant. From affinity to less affinity:9
- D4 receptors
- DRD4-2R
- DRD4-4R
- DRD4-7R
- D2 receptors
- D2 short
- D2 long
- D2-D4 receptor heteromers
D3 and D5 receptors are high-affinity, D1 and D2 receptors low-affinity on dopamine.10 The earlier model that D1 is low-affinity and D2 is high-affinity is outdated.
6.3. Dopamine receptors mostly extrasynaptic
Like DAT, which is critical for dopamine reuptake, most dopamine receptors-including the D2 autoreceptor-are located extrasynaptically rather than within synapses.11
6.4. D1-like dopamine receptors: activating
D1R-like receptors (D1R and D5R) generally couple to the Gs/olf proteins that stimulate adenylate cyclase (AC). Adenylate cyclase is an enzyme that converts adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP). cAMP activates protein kinase A (PKA), which in turn phosphorylates cAMP response element-binding protein (CREB). CREB translocates to the nucleus and activates CREB-dependent transcription of genes involved in synaptic plasticity. D1R modulate several ion channels, including voltage-activated Na+, K+, and Ca2+ channels, as well as the G-protein gated inwardly rectifying K+ channel (GIRK).212 [15,16,17,18].
6.4.1. D1 receptor
- Low affinity10
- Anti-inflammatory (neuroinflammation)10
- Postsynaptic
- Activating
when dopamine binds to receptors D1 or D5, the respective downstream synapse is activated = depolarized (excitatory postsynaptic potential) - Appearance:
- Nucleus accumbens (ventral striatum) (together with D3 receptors)141314
- Olfactory bulb14
- Basal Ganglia14
- Hypothalamus
- Thalamus
- (only) in projections (without mRNA) from striatal GABAergic cells that simultaneously produce substance P,
in- Entopeduncular nucleus
- Globus pallidus
- Substantia nigra pars reticulata
- Lower also in the PFC14
- Agonists:
- Antagonists:
Involved in the formation of aversive memories.
In mPFC pyramidal neurons, D1 receptors on dendritic spines and D5 receptors on dendritic shafts are more prominent. Simultaneous pharmacological activation of D1 and D5 receptors in mPFC by the D1 and D5 agonist SKF-38393 promoted the development of aversive memories.16
After birth, the density of D1 and D2 receptors in the striatum initially increases. In adolescence, the number of these receptors decreases to 40% of the initial level.17 This decrease is again significantly greater in males than in females.
High expression of dopamine transporters could potentially result in increased expression of D1, D2, and VMAT2 receptors.18
Glucocorticoids cause sensitization of D1 receptors in GABAergic cells of the striatum in rats,1920 as well as stress.2122
6.4.2. D5 receptor
Involved in the formation of aversive memories.
In mPFC pyramidal neurons, D1 receptors on dendritic spines and D5 receptor on dendritic shafts are more prominent. Simultaneous pharmacological activation of D1 and D5 receptors in mPFC by the D1 and D5 agonist SKF-38393 promotes the generation of aversive memories.16
- High affinity10
- Pro-inflammatory (neuroinflammation)10
- Postsynaptic
- Activating: if dopamine binds to the receptors D1 or D5, the respective following synapse is activated = depolarized (excitatory postsynaptic potential)
- Appearance:
- Agonists:
- Antagonists:
6.5. D2-like dopamine receptors: inhibitory
D2R-like receptors (D2R, D3R, and D4R) induce by coupling to Gi/o proteins:223
- The inhibition of AC- and PKA-dependent signaling pathways
- The activation of GIRK
- The closure of voltage-activated Ca2+ channels.
For activation or deactivation of the subsequent synapse, a certain percentage of the activating or inhibiting (here: dopamine) receptors must be initiated by means of dopamine binding. If there is too little dopamine in the synaptic cleft due to the overactivity of the dopamine reuptake transporters, not enough receptors are initiated. As a result, the activation / deactivation of the subsequent synapse, which is actually due, fails to occur.
It is interesting to note that the brain makes the decision to act up to 7 seconds before the person becomes aware of the decision itself. These 7 seconds are available to the person to still suppress an already “made” decision - by means of inhibitory deactivation of the synapses that pass on the decision. Still 200 milliseconds before the execution, the person can cancel the already made decision.24
Figuratively, one brain area puts intended decisions “up for discussion” and gives other brain regions the opportunity to evaluate and allow or disallow them.
This testing and aborting mechanism is controlled to a large extent by dopamine. If the dopamine control circuit is disturbed, the mechanism that leads to the termination of adverse decisions is inhibited.
6.5.1. D2 receptor
- Low affinity,10 at least in vivo as low affinity as D11
- No activation by basal dopamine levels (2 to 20 nM)
- Activation at 100 μM by phasic dopamine release
- Anti-inflammatory (neuroinflammation)10
- Presynaptic and postsynaptic
- 2 Isoforms25
- D2 short receptors can function as autoreceptors
-
Inhibitory feedback mechanism by modifying26
- DA synthesis
- DA release
- DA recovery
in response to increasing amounts of extracellular synaptic dopamine.
- Presynaptic D2 autoreceptors are 6 times more affine to dopamine than postsynaptic D2 receptors
- D2 autoreceptors on dopamine axons respond to tonic and phasic dopamine2728
- Your activation
- Inhibits dopamine synthesis
- Increases dopamine uptake
- Regulates VMAT2 expression29
- Your activation
- D2 autoreceptors in the soma
- Activation inhibits firing of dopamine neurons30
-
Inhibitory feedback mechanism by modifying26
-
Inhibiting:
when dopamine binds to receptors D2, D3 or D4, the respective following synapse is inhibited = polarized (inhibitory postsynaptic potential)- Inhibits adenylyl cyclase13
- Inhibits cAMP production
- D2 short inhibits cAMP more effectively and requires fewer agonists for this purpose than D2 long13
- Enhances ATP- or calcium ionophore-induced arachidonic acid release in CHO cells13
- Increases the intracellular calcium level in13
- Ltk cells
- Due to increased PI hydrolysis
- CCL1.3 cells
- Due to increased PI hydrolysis
- CHO cells
- But not by increased PI hydrolysis
- Ltk cells
- The more dopamine receptors present, the greater the acetylcholinergic excess that occurs if these receptors are blocked.
- The administration of typical antipsychotics (= typical neuroleptics, e.g. haloperidol), which block the postsynaptic dopamine D2 receptors as D2 antagonists, causes pronounced acetylcholinergic side effects such as extrapyramidal symptoms or akathisia (taskinesia, restlessness) in patients with a high number of dopamine receptors. The acetylcholinergic excess in sufferers with a high number of dopamine receptors explains the frequent use of anticholinergic and sedating substances as well as the frequent use of cocaine.
- Appearance:
-
Striatum (together with D1 receptors)14
- Expressed by GABAergic neurons, which at the same time express enkephalins13
- D2 are also expressed on dopamine axons
- Olfactory bulb14
- Expressed by GABAergic neurons, which at the same time express enkephalins13
-
Nucleus accumbens 14
- Expressed by GABAergic neurons, which at the same time express enkephalins13
-
Substantia nigra pars compacta
- Expressed by dopaminergic neurons13
-
Ventral tegmentum
- Expressed by dopaminergic neurons13
- Adrenal gland
- Here the D2 receptor regulates the production and release of PRL
-
Striatum (together with D1 receptors)14
- Agonists
- Antagonists:
-
Antagonist and agonist
- Aripiprazole33
- D2 receptor partial agonism
- Acts as an antagonist in the case of dopamine excess and as an agonist in the case of dopamine deficiency.
Has an inhibitory effect against dopaminergic hyperfunction in the mesolimbic system and an activating effect against dopaminergic hypofunction in the mesocortical system. Thus low risk of excessive D2 receptor blockade in striatum or pituitary gland
- Acts as an antagonist in the case of dopamine excess and as an agonist in the case of dopamine deficiency.
- Serotonin 5-HT1A receptor partial agonism
- 5-HT2A receptor antagonism
- Only very weak prolactin agonist
- Outreach. Schizophrenia
- D2 receptor partial agonism
- D2-, D3- and D4- receptors act
- Prolactin activating
- Acetylcholine inhibiting
- Aripiprazole33
- Poisons
- Reduction of D2 receptors by34
- Pesticides
- Mercury
- Formaldehyde
- Reduction of D2 receptors by34
Blockade of D2 receptors leads to an increase in dopamine levels.35
After birth, the density of D1 and D2 receptors in the striatum initially increases. The increase in D2 receptors after birth is more pronounced in males than in females.36
In adolescence, the number of these receptors drops to 40% of the initial level.17 This decrease is again significantly greater in males than in females.
With age, the density of D2 receptors in the striatum decreases.37
High expression of dopamine transporters could possibly result in increased expression of D1 receptors, D2 receptors, and VMAT2 receptors.18
A rather small study of children with ADHD (quite a few of whom experience prematurity or were born with low weight) found evidence of lower D2/D3 receptor binding/number in ADHD-C sufferers than in ADHD-I subtype sufferers: ADHD-C: 2.9 (2.6 - 3.5); ADHD-I: 4.0 (3.3 - 4.5).38
D2 and D3 agonists increase cataplexy (narcolepsy symptom), D2 and D3 antagonists decrease it.39
D2 and D3 agonists do not appear to affect REM sleep.39
6.5.3. D3 receptor
- High affinity10
- Pro-inflammatory (neuroinflammation)10
- Presynaptic and postsynaptic
-
Inhibiting:
when dopamine binds to receptors D2, D3 or D4, the respective following synapse is inhibited = polarized (inhibitory postsynaptic potential)- Inhibits adenylyl cyclases
- Lower than D2 receptors in13
- CHO 10001 cells
- 293 cells
- NG108-15 cells
- And not at all in
- GH4C1 cells
- MN9D cells
- SK-N-MC cells
- CHO cl cells
- NG108-15 cells
- CCL1.3 Cells
- Lower than D2 receptors in13
- At least in CHO cells or GH4CI cells, no enhancement of ATP- or calcium ionophore-induced arachidonic acid release was observed13
- No stimulation of PI hydrolysis13
- Inhibits adenylyl cyclases
- Appearance
- Predominantly in the limbic system4014
- Nucleus accumbens
- Olfactory bulb
-
Cerebellum
- Since the cerebellum is not connected to other brain areas via dopaminergic projections (communication pathways), D3 receptors are thought to exert nonsynaptic dopaminergic functions here
- Islands of Calleja (a group of densely packed small cells in the cortex of the hippocampal gyrus)
- Low in the nucleus accumbens (ventral striatum)32
- D3 receptor agonists
- Quinpirole13
- 7-OH-DPAT13
- Apormophine13
- Pramipexole, (S)-2-amino-4,5,6,7-tetrahydro-6-(propylamino)benzothiazole; (S)-2-amino-6-(propylamino)-4,5,6,7-tetrahydrobenzothiazole
- Ropinirole, 4-[2-(dipropylamino)ethyl]indolin-2-one
- (+)-PD12890731
-
Norepinephrine25
- Norepinephrine has different affinity on D2-type receptors: D3R > D4R ≥ D2SR ≥ D2L
- Antagonists:
D2 and D3 agonists increase cataplexy (narcolepsy symptom), D2 and D3 antagonists decrease it.39
D2 and D3 agonists do not appear to affect REM sleep.39
6.5.4. D4 receptor
D4 receptors are involved in encoding the memory of fear, but not in encoding the memory of reward.16
- Rather high affinity
- Presynaptic and postsynaptic
-
Inhibiting:
when dopamine binds to receptors D2, D3 or D4, the respective following synapse is inhibited = polarized (inhibitory postsynaptic potential) - Appearance:
- Agonists
- Antagonists:
6.6. Heteromeric
Dopamine receptors form pure dopaminergic heteromers as well as heteromers with other receptor families, e.g.:
- D1 / D2 - Heterodimers44
- D1 / D3 - Heterodimers45
- Adenosine A2A / D2 - heterodimers appear to be partially responsible for the psychomotor and reinforcing effects of psychostimulants such as cocaine and amphetamine.46
- Cannabinoid CB1 / D2 - Heterodimers in the striatum47
- Cannabinoid-CB1 / Adenosine-2A / D2 - Heretotrimers4849
- Adenosine-2A / D2 / glutamate Metabotropic mGlu(5) - Heterotrimers in the striatum50
6.7. G protein-independent dopamine receptor activation
DA receptors can also be activated by mechanisms independent of G proteins. This may be mediated by the multifunctional adaptor protein arrestin, which binds DA receptors phosphorylated by GPCR kinases (GRKs) and recruits several proteins, including Akt, GSK-3, MAPK, c-Src, Mdm2, and N-ethylmaleimide-sensing factor. Binding of arrestin to active phosphorylated receptors halts further activation of G proteins and promotes endocytosis of the receptor. In mammals, there are seven GRKs: GRK2, GRK3, GRK4, GRK5, and GRK6 regulate D1R and D2R, while GRK4 controls D3R. In the striatum, GRKs 2, 3, 5, and 6 are expressed with different expression levels and different cellular and subcellular distribution.251
6.8. Dopamine agonists and antagonists
6.8.1. Dopamine agonists
- Apomorphine31
- FAUC 17931
- Budipin, 1-tert-butyl-4,4-diphenylpiperidine
- Dopamine receptor agonist
- NMDA receptor antagonist
- MAO inhibitor antagonist
- Weak anticholinergic effect
- Cabergoline, 1-[(6-allyl-8beta-yl)carbonyl]-1-[3-(dimethylamino)propyl]-3-ethylurea; 1[(6-allyl-8-beta-ergolinyl)carbonyl]-1-[3-(dimethylamino)propyl]-3-ethylurea, N-[3-(dimethylamino)propyl]-N-[(ethylamino)carbonyl]-6-(prop-2-enyl)-8beta-ergoline-8-carboxamide
- Dopamine receptor agonist
- Prolactin antagonist
- Dihydroergocryptine, 9,10-dihydro-12-hydroxy-2-isopropyl-5 alpha-(2-methylpropyl)ergotaman-3,6,18-trione
- Dopamine receptor agonist
- Levodopa
- Dopamine / norepinephrine / epinephrine - prodrug
- Carbidopa
- Lisuride, 1,1-diethyl-3-(6-methyl-9,10-didehydroergolin-8alpha-yl)urea
- Dopamine receptor agonist
- Prolactin antagonist
- Influence on growth hormone
- Pergolide, 8beta-(methylthiomethyl)-6-propylergoline
- Dopamine receptor agonist
- Piribedil, 2-[4-(1,3-benzodioxol-5-ylmethyl)piperazin-1-yl]pyrimidine. Piperazidine. Piprazidine
- Dopamine receptor agonist
- Acetylcholine receptor antagonist
- Pramipexole, (S)-2-amino-4,5,6,7-tetrahydro-6-(propylamino)benzothiazole. (S)-2-amino-6-(propylamino)-4,5,6,7-tetrahydrobenzothiazole
- D3 dopamine receptor agonist31
- Ropinirole, 4-[2-(dipropylamino)ethyl]indolin-2-one
- D3 dopamine receptor agonist31
- 5,6,7,8-Tetrahydro-6-(2-propen-1-yl)-4H-thiazolo[4,5-d]azepin-2-amin Dihydrochlorid (BHT-920)
- D2 agonist52
6.8.2. Indirect dopamine receptor agonists
Indirect dopamine receptor agonists increase (via different mechanisms) the activity of the mesolimbic dopaminergic system:
6.8.3. Dopamine antagonists
- Paliperidon, (RS)-3-{2-[4-(6-Fluor-1,2-benzisoxazol-3-yl)piperidino]ethyl}-9-hydroxy-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-on; 9-Hydroxy-Risperidon
- Dopamine antagonist
- Norepinephrine antagonist
- Adrenaline antagonist
- Serotonin antagonist
- Histamine antagonist
- Adenosine
- Dopamine Inhibitors
Liu, Goel, Kaeser (2021): Spatial and temporal scales of dopamine transmission. Nat Rev Neurosci. 2021 Jun;22(6):345-358. doi: 10.1038/s41583-021-00455-7. PMID: 33837376; PMCID: PMC8220193. ↥ ↥
Speranza, di Porzio, Viggiano, de Donato, Volpicelli (2021): Dopamine: The Neuromodulator of Long-Term Synaptic Plasticity, Reward and Movement Control. Cells. 2021 Mar 26;10(4):735. doi: 10.3390/cells10040735. PMID: 33810328; PMCID: PMC8066851. REVIEW ↥ ↥ ↥ ↥
Gatzke-Kopp, Beauchaine (2007): Central nervous system substrates of impulsivity: Implications for the development of attention-deficit/hyperactivity disorder and conduct disorder. In: Coch, Dawson, Fischer ( Eds): Human behavior, learning, and the developing brain: Atypical development. New York: Guilford Press; 2007. pp. 239–263; 245 ↥
Edel, Vollmoeller (2006): ADHS bei Erwachsenen, Seite 112 ↥
Araki, Sims, Bhide (2007): Dopamine receptor mRNA and protein expression in the mouse corpus striatum and cerebral cortex during pre- and postnatal development. Brain Res. 2007 Jul 2;1156:31-45. doi: 10.1016/j.brainres.2007.04.043. PMID: 17509542; PMCID: PMC1994791. ↥
Perreault, Hasbi, O’Dowd, George (2014): Heteromeric dopamine receptor signaling complexes: emerging neurobiology and disease relevance. Neuropsychopharmacology. 2014 Jan;39(1):156-68. doi: 10.1038/npp.2013.148. PMID: 23774533; PMCID: PMC3857642. ↥
Meador-Woodruff, Damask, Wang, Haroutunian, Davis, Watson (1996): Dopamine receptor mRNA expression in human striatum and neocortex. Neuropsychopharmacology. 1996 Jul;15(1):17-29. doi: 10.1016/0893-133X(95)00150-C. PMID: 8797188. ↥
Stahl (2000): Essential Psychopharmacology, Neuroscientific Basis and Practical Applications. Second Edition, Cambridge University Press; zitiert nach Franck (2003): Hyperaktivität und Schizophrenie – eine explorative Studie; Dissertation, Seite 66 ↥
Bonaventura, Quiroz, Cai, Rubinstein, Tanda, Ferré (2017): Key role of the dopamine D4 receptor in the modulation of corticostriatal glutamatergic neurotransmission. Sci Adv. 2017 Jan 11;3(1):e1601631. doi: 10.1126/sciadv.1601631. eCollection 2017 Jan. ↥
Broome, Louangaphay, Keay, Leggio, Musumeci, Castorina (2020): Dopamine: an immune transmitter. Neural Regen Res. 2020 Dec;15(12):2173-2185. doi: 10.4103/1673-5374.284976. PMID: 32594028; PMCID: PMC7749467. REVIEW ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥
Pereira, Sulzer (2012): Mechanisms of dopamine quantal size regulation. Front Biosci (Landmark Ed). 2012 Jun 1;17(7):2740-67. doi: 10.2741/4083. PMID: 22652810. REVIEW ↥
Gurevich, Gainetdinov, Gurevich (2016): G protein-coupled receptor kinases as regulators of dopamine receptor functions. Pharmacol Res. 2016 Sep;111:1-16. doi: 10.1016/j.phrs.2016.05.010. PMID: 27178731; PMCID: PMC5079267. ↥
Jaber, Robinson, Missale, Caron (1996): Dopamine receptors and brain function; Neuropharmacology; Volume 35, Issue 11, 1996, Pages 1503-1519; https://doi.org/10.1016/S0028-3908(96)00100-1 ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥
Stuckenholz (2013): Die Effekte des α7-nikotinergen Acetylcholin-Agonisten PNU-282987 und des nikotinergen Acetylcholin-Antagonisten Mecamylamin auf Neuroinflammation und Neurodegeneration im akuten MPTP-Mausmodell des Morbus Parkinson, Dissertation ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥
Weele, Siciliano, Tye (2018): Dopamine tunes prefrontal outputs to orchestrate aversive processing. Brain Res. 2018 Dec 1. pii: S0006-8993(18)30610-3. doi: 10.1016/j.brainres.2018.11.044. Seite 31 ↥ ↥ ↥
Franck (2003): Hyperaktivität und Schizophrenie – eine explorative Studie; Dissertation, unter Verweis auf Seeman 1987 ↥ ↥
Reinel (2015): Multidisziplinäre Untersuchung dopaminerger Mechanismen der repetitiven Störungen anhand von zwei Rattenmodellen dopaminerger Dysregulation, Dissertation ↥ ↥
Schoffelmeer, De Vries, Vanderschuren, Tjon, Nestby, Wardeh, Mulder (1997): Intermittent morphine administration induces a long-lasting synergistic effect of corticosterone on dopamine D1 receptor functioning in rat striatal GABA neurons. Synapse. 1997 Apr;25(4):381-8. doi: 10.1002/(SICI)1098-2396(199704)25:4<381::AID-SYN9>3.0.CO;2-6. PMID: 9097397. ↥
Schoffelmeer, De Vries, Vanderschuren, Tjon, Nestby, Wardeh, Mulder (1995): Glucocorticoid receptor activation potentiates the morphine-induced adaptive increase in dopamine D-1 receptor efficacy in gamma-aminobutyric acid neurons of rat striatum/nucleus accumbens. J Pharmacol Exp Ther. 1995 Sep;274(3):1154-60. PMID: 7562482. ↥
Gariépy, Gendreau, Cairns, Lewis (1998): D1 dopamine receptors and the reversal of isolation-induced behaviors in mice. Behav Brain Res. 1998 Sep;95(1):103-11. doi: 10.1016/s0166-4328(97)00215-5. PMID: 9754882. ↥
Gariépy, Gendreau, Mailman, Tancer, Lewis (1995): Rearing conditions alter social reactivity and D1 dopamine receptors in high- and low-aggressive mice. Pharmacol Biochem Behav. 1995 Aug;51(4):767-73. doi: 10.1016/0091-3057(95)00028-u. PMID: 7675857. ↥
Missale, Nash, Robinson, Jaber, Caron (1998): Dopamine receptors: from structure to function. Physiol Rev. 1998 Jan;78(1):189-225. doi: 10.1152/physrev.1998.78.1.189. PMID: 9457173. REVIEW ↥
Interview mit John-Dylan Haynes in Technologie Report Heft 04 2016, Seite 46 ↥
Sánchez-Soto, Bonifazi, Cai, Ellenberger, Newman, Ferré, Yano (2016): Evidence for Noncanonical Neurotransmitter Activation: Norepinephrine as a Dopamine D2-Like Receptor Agonist. Mol Pharmacol. 2016 Apr;89(4):457-66. doi: 10.1124/mol.115.101808. ↥ ↥ ↥ ↥
Lee, Pei, Moszczynska, Vukusic, Fletcher, Liu (2007): Dopamine transporter cell surface localization facilitated by a direct interaction with the dopamine D2 receptor. EMBO J. 2007;26(8):2127–2136. doi:10.1038/sj.emboj.7601656 ↥ ↥ ↥
Marcott, Gong, Donthamsetti, Grinnell, Nelson, Newman, Birnbaumer, Martemyanov, Javitch, Ford (2018): Regional Heterogeneity of D2-Receptor Signaling in the Dorsal Striatum and Nucleus Accumbens. Neuron. 2018 May 2;98(3):575-587.e4. doi: 10.1016/j.neuron.2018.03.038. PMID: 29656874; PMCID: PMC6048973. ↥
Marcott, Mamaligas, Ford (2014): Phasic dopamine release drives rapid activation of striatal D2-receptors. Neuron. 2014 Oct 1;84(1):164-176. doi: 10.1016/j.neuron.2014.08.058. PMID: 25242218; PMCID: PMC4325987. ↥
Sulzer, Cragg, Rice (2016): Striatal dopamine neurotransmission: regulation of release and uptake. Basal Ganglia. 2016 Aug;6(3):123-148. doi: 10.1016/j.baga.2016.02.001. PMID: 27141430; PMCID: PMC4850498. ↥
Beckstead, Grandy, Wickman, Williams (2004): Vesicular dopamine release elicits an inhibitory postsynaptic current in midbrain dopamine neurons. Neuron. 2004 Jun 24;42(6):939-46. doi: 10.1016/j.neuron.2004.05.019. PMID: 15207238. ↥
Frank (2005): Synthese von dualen NMDA-Rezeptor-/Dopamin-Rezeptor-Liganden, Dissertation, Seite 31 ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥
Frank (2005): Synthese von dualen NMDA-Rezeptor-/Dopamin-Rezeptor-Liganden, Dissertation, Seite 33 ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥
Wolf, Calabrese (2020): Stressmedizin & Stresspsychologie; Seite 302 ↥
Böhm (2020): Dopaminerge Systeme, in: Freissmuth, Offermanns, Böhm (Herausgeber): Pharmakologie und Toxikologie. Von den molekularen Grundlagen zur Pharmakotherapie. ↥
Franck (2003): Hyperaktivität und Schizophrenie – eine explorative Studie; Dissertation, unter Verweis auf Anderson und Teicher, 2000 ↥
Rinne, Hietala, Ruotsalainen, Säkö, Laihinen, Någren, Lehikoinen, Oikonen, Syvälahti (1993): Decrease in human striatal dopamine D2 receptor density with age: a PET study with [11C]raclopride. J Cereb Blood Flow Metab. 1993 Mar;13(2):310-4. doi: 10.1038/jcbfm.1993.39. PMID: 8436624. ↥
Rosa-Neto, Lou, Cumming, Pryds, Karrebaek, Lunding, Gjedde (2005): Methylphenidate-evoked changes in striatal dopamine correlate with inattention and impulsivity in adolescents with attention deficit hyperactivity disorder. Neuroimage. 2005 Apr 15;25(3):868-76. doi: 10.1016/j.neuroimage.2004.11.031. PMID: 15808987. n = 9 ↥
Nishino, Sakai (2016): Modulations of Ventral Tegmental Area (VTA) Dopaminergic Neurons by Hypocretins/Orexins: Implications in Vigilance and Behavioral Control In: Monti, Pandi-Perumal, Chokroverty (Herausgeber) (2016): Dopamine and Sleep: Molecular, Functional, and Clinical Aspects, 65-90, 74 ↥ ↥ ↥ ↥
Frank (2005): Synthese von dualen NMDA-Rezeptor-/Dopamin-Rezeptor-Liganden, Dissertation, Seite 34 ↥ ↥ ↥
Roessner, Rothenberger (2020): Neurochemie, S. 94, in Steinhausen, Rothenberger, Döpfner (Herausgeber): Handbuch ADHS; Grundlagen, Klinik, Therapie und Verlauf der Aufmerksamkeitsdefizit-Hyperaktivitätsstörung, Kohlhammer ↥
Einsiedel, Hübner, Gmeiner (2001): Benzamide bioisosteres incorporating dihydroheteroazole substructures: EPC synthesis and SAR leading to a selective dopamine D4 receptor partial agonist (FAUC 179), Bioorganic & Medicinal Chemistry Letters, Volume 11, Issue 18, 17 September 2001, Pages 2533-2536 https://doi.org/10.1016/S0960-894X(01)00484-XII ↥
Raviña, Casariego, Masaguer, Fontenla, Montenegro, Rivas, Loza, Enguix, Villazon, Cadavid, Demontis (2000): Conformationally Constrained Butyrophenones with Affinity for Dopamine (D1, D2, D4) and Serotonin (5-HT2A, 5-HT2B, 5-HT2C) Receptors: Synthesis of Aminomethylbenzo[b]furanones and Their Evaluation as Antipsychotics; Journal of Medicinal Chemistry 2000 43 (24), 4678-4693; DOI: 10.1021/jm0009890 ↥
Rashid, So, Kong, Furtak, El-Ghundi, Cheng, O’Dowd, George (2007): D1-D2 dopamine receptor heterooligomers with unique pharmacology are coupled to rapid activation of Gq/11 in the striatum. Proc Natl Acad Sci U S A. 2007 Jan 9;104(2):654-9. doi: 10.1073/pnas.0604049104. PMID: 17194762; PMCID: PMC1766439. ↥
Marcellino, Ferré, Casadó, Cortés, Le Foll, Mazzola, Drago, Saur, Stark, Soriano, Barnes, Goldberg, Lluis, Fuxe, Franco (2008): Identification of dopamine D1-D3 receptor heteromers. Indications for a role of synergistic D1-D3 receptor interactions in the striatum. J Biol Chem. 2008 Sep 19;283(38):26016-25. doi: 10.1074/jbc.M710349200. PMID: 18644790; PMCID: PMC2533781. ↥
Ballesteros-Yáñez, Castillo, Merighi, Gessi (2016): The Role of Adenosine Receptors in Psychostimulant Addiction. Front Pharmacol. 2018 Jan 10;8:985. doi: 10.3389/fphar.2017.00985. PMID: 29375384; PMCID: PMC5767594. ↥
Marcellino, Carriba, Filip, Borgkvist, Frankowska, Bellido, Tanganelli, Müller, Fisone, Lluis, Agnati, Franco, Fuxe (2008): Antagonistic cannabinoid CB1/dopamine D2 receptor interactions in striatal CB1/D2 heteromers. A combined neurochemical and behavioral analysis. Neuropharmacology. 2008 Apr;54(5):815-23. doi: 10.1016/j.neuropharm.2007.12.011. PMID: 18262573. ↥
Carriba, Navarro, Ciruela, Ferré, Casadó, Agnati, Cortés, Mallol, Fuxe, Canela, Lluís, Franco (2008): Detection of heteromerization of more than two proteins by sequential BRET-FRET. Nat Methods. 2008 Aug;5(8):727-33. doi: 10.1038/nmeth.1229. PMID: 18587404. ↥
Ferré, Goldberg, Lluis, Franco (2008): Looking for the role of cannabinoid receptor heteromers in striatal function. Neuropharmacology. 2009;56 Suppl 1(Suppl 1):226-34. doi: 10.1016/j.neuropharm.2008.06.076. PMID: 18691604; PMCID: PMC2635338. ↥
Ferré, Agnati, Ciruela, Lluis, Woods, Fuxe, Franco (2007): Neurotransmitter receptor heteromers and their integrative role in ‘local modules’: the striatal spine module. Brain Res Rev. 2007 Aug;55(1):55-67. doi: 10.1016/j.brainresrev.2007.01.007. PMID: 17408563; PMCID: PMC2039920. ↥
Yang (2021): Functional Selectivity of Dopamine D1 Receptor Signaling: Retrospect and Prospect. Int J Mol Sci. 2021 Nov 3;22(21):11914. doi: 10.3390/ijms222111914. PMID: 34769344; PMCID: PMC8584964. REVIEW ↥
Prasad, de Vries, Elsinga, Dierckx, van Waarde (2021): Allosteric Interactions between Adenosine A2A and Dopamine D2 Receptors in Heteromeric Complexes: Biochemical and Pharmacological Characteristics, and Opportunities for PET Imaging. Int J Mol Sci. 2021 Feb 9;22(4):1719. doi: 10.3390/ijms22041719. PMID: 33572077; PMCID: PMC7915359. REVIEW ↥