The Physiology, Signaling, and Pharmacology of Dopamine Receptors

Beaulieu, Jean‐Martin; Gainetdinov, Raul R.

doi:10.1124/pr.110.002642

Cited by 2,287 publications

(2,288 citation statements)

References 395 publications

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“…The molecular and cellular mechanisms that facilitate neurotransmission in the mesolimbic DA reward pathway involve the cellular elements modulating synaptic DA neurotransmission, including neurotransmitters, transporters, receptors, G proteins, second-messenger-generating enzymes, ion channels, and immediate early response genes that regulate neuronal functions (Figure 2) [65-67]. Afferents from the VTA of the mesolimbic DA system project outward, and primarily terminate onto the MSNs, which are the principal cell type in the NAc, and produce and secrete GABA, the main inhibitory neurotransmitter used in the CNS.…”

Section: Reviewmentioning

confidence: 99%

“…Neurotransmission of the DA signal to MSNs in the NAc is mediated by binding to specific DA receptors. These DA receptors are part of the Gprotein-coupled receptor superfamily, and upon binding DA, activate heterotrimeric G proteins (Golf/Gs or Gi/o) that in turn regulate the activity of effector proteins such as ion channels, or the enzyme adenylyl cyclase that produces the second messenger cAMP [65]. Five distinct DA receptors (D 1 to D 5 ) can mediate neurotransmission, and are coupled positively to activation of adenylyl cyclase (D 1 and D 5 receptors) or negatively to inhibition of adenylyl cyclase (D 2 , D 3 , D 4 ).…”

Section: Reviewmentioning

confidence: 99%

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Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings

Dichter

Damiano

Allen

2012

J Neurodevelop Disord

254

207

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This review summarizes evidence of dysregulated reward circuitry function in a range of neurodevelopmental and psychiatric disorders and genetic syndromes. First, the contribution of identifying a core mechanistic process across disparate disorders to disease classification is discussed, followed by a review of the neurobiology of reward circuitry. We next consider preclinical animal models and clinical evidence of reward-pathway dysfunction in a range of disorders, including psychiatric disorders (i.e., substance-use disorders, affective disorders, eating disorders, and obsessive compulsive disorders), neurodevelopmental disorders (i.e., schizophrenia, attention-deficit/hyperactivity disorder, autism spectrum disorders, Tourette’s syndrome, conduct disorder/oppositional defiant disorder), and genetic syndromes (i.e., Fragile X syndrome, Prader–Willi syndrome, Williams syndrome, Angelman syndrome, and Rett syndrome). We also provide brief overviews of effective psychopharmacologic agents that have an effect on the dopamine system in these disorders. This review concludes with methodological considerations for future research designed to more clearly probe reward-circuitry dysfunction, with the ultimate goal of improved intervention strategies.

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Section: Reviewmentioning

confidence: 99%

Section: Reviewmentioning

confidence: 99%

Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings

Dichter

Damiano

Allen

2012

J Neurodevelop Disord

254

207

View full text Add to dashboard Cite

show abstract

“…Generally, there are two subgroups of DA receptors: the D1-like and D2-like families. The D1-like family is expressed at high density in the frontal cortex, striatum, nucleus accumbens, and substantia nigra; the D2-like family is at high levels also in the striatum, nucleus accumbems, and substantia nigra, as well as in the olfactory tubercle and other cortical areas [14] .…”

Section: Introductionmentioning

confidence: 99%

Interactive effects of morphine and dopaminergic compounds on spatial working memory in rhesus monkeys

et al. 2013

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Opiates and dopamine (DA) play key roles in learning and memory in humans and animals. Although interactions between these neurotransmitters have been found, their functional roles remain to be fully elucidated, and their dysfunction may contribute to human diseases and addiction. Here we investigated the interactions of morphine and dopaminergic neurotransmitter systems with respect to learning and memory in rhesus monkeys by using the Wisconsin General Test Apparatus (WGTA) delayed-response task. Morphine and DA agonists (SKF-38393, apomorphine and bromocriptine) or DA antagonists (SKF-83566, haloperidol and sulpiride) were co-administered to the monkeys 30 min prior to the task. We found that dose-patterned co-administration of morphine with D1 or D2 antagonists or agonists reversed the impaired spatial working memory induced by morphine or the compounds alone. For example, morphine at 0.01 mg/kg impaired spatial working memory, while morphine (0.01 mg/kg) and apomorphine (0.01 or 0.06 mg/kg) co-treatment ameliorated this effect. Our findings suggest that the interactions between morphine and dopaminergic compounds influence spatial working memory in rhesus monkeys. A better understanding of these interactive relationships may provide insights into human addiction.

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“…Increased extracellular DA in the dopaminergic mesocorticolimbic and nigrostriatal systems plays a critical role in the effects of cocaine and addiction [1] . DA acts through DA receptors, which can be grouped into two subclasses based on their structural, pharmacological, and physiological properties [4] . The D1-like subclass is composed of D1 and D5 receptors that couple to the G s / adenylate cyclase/cyclic adenosine 3,5,-monophosphate (cAMP) signaling pathway.…”

Section: Introductionmentioning

confidence: 99%

“…To date, three classes of protein kinases have been identified to be involved in D1R phosphorylation: G-protein-coupled receptor kinases (GRKs), cAMP-dependent protein kinase (PKA), and protein kinase C (PKC) [4] . The major effect of D1R phosphorylation is receptor desensitization, the process of diminishing receptor responsiveness under continuous agonist stimulation.…”

Section: Introductionmentioning

confidence: 99%

Disruption of dopamine D1 receptor phosphorylation at serine 421 attenuates cocaine-induced behaviors in mice

Zhang

Wang

et al. 2014

Neurosci. Bull.

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Dopamine D1 receptors (D1Rs) play a key role in cocaine addiction, and multiple protein kinases such as GRKs, PKA, and PKC are involved in their phosphorylation. Recently, we reported that protein kinase D1 phosphorylates the D1R at S421 and promotes its membrane localization. Moreover, this phosphorylation of S421 is required for cocaineinduced behaviors in rats. In the present study, we generated transgenic mice over-expressing S421A-D1R in the forebrain. These transgenic mice showed reduced phospho-D1R (S421) and its membrane localization, and reduced downstream ERK1/2 activation in the striatum. Importantly, acute and chronic cocaine-induced locomotor hyperactivity and conditioned place preference were significantly attenuated in these mice. These fi ndings provide in vivo evidence for the critical role of S421 phosphorylation of the D1R in its membrane localization and in cocaine-induced behaviors. Thus, S421 on the D1R represents a potential pharmacotherapeutic target for cocaine addiction and other drug-abuse disorders.

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The Physiology, Signaling, and Pharmacology of Dopamine Receptors

Cited by 2,287 publications

References 395 publications

Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings

Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings

Interactive effects of morphine and dopaminergic compounds on spatial working memory in rhesus monkeys

Disruption of dopamine D1 receptor phosphorylation at serine 421 attenuates cocaine-induced behaviors in mice

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