The Physiology, Signaling, and Pharmacology of Dopamine Receptors

Pharmacological Reviews, Journal Year: 2011, Volume and Issue: 63(1), P. 182 - 217

Published: Feb. 8, 2011

G protein-coupled dopamine receptors (D1, D2, D3, D4, and D5) mediate all of the physiological functions catecholaminergic neurotransmitter dopamine, ranging from voluntary movement reward to hormonal regulation hypertension. Pharmacological agents targeting dopaminergic neurotransmission have been clinically used in management several neurological psychiatric disorders, including Parkinson9s disease, schizophrenia, bipolar disorder, Huntington9s attention deficit hyperactivity disorder (ADHD¹), Tourette9s syndrome. Numerous advances occurred understanding general structural, biochemical, functional properties that led development multiple pharmacologically active compounds directly target receptors, such as antiparkinson drugs antipsychotics. Recent progress complex biology receptor-related signal transduction mechanisms has revealed that, addition their primary action on cAMP-mediated signaling, can act through diverse signaling involve alternative protein coupling or protein-independent via interactions with ion channels proteins are characteristically implicated receptor desensitization, β-arrestins. One future directions managing dopamine-related pathologic conditions may a transition approaches affect function precise postreceptor intracellular modalities either ligand-biased pharmacology. In this comprehensive review, we discuss classification, basic structural genetic organization, distribution brain periphery, mechanisms. addition, abnormalities expression, function, documented human disorders current pharmacology emerging trends novel therapeutic at and/or related events.

Language: Английский

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Epigenetic regulation in psychiatric disorders

Nature reviews. Neuroscience, Journal Year: 2007, Volume and Issue: 8(5), P. 355 - 367

Published: April 24, 2007

Language: Английский

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REVIEW ON CPP: Measuring reward with the conditioned place preference (CPP) paradigm: update of the last decade

Addiction Biology, Journal Year: 2007, Volume and Issue: 12(3-4), P. 227 - 462

Published: July 30, 2007

ABSTRACT Conditioned place preference (CPP) continues to be one of the most popular models study motivational effects drugs and non‐drug treatments in experimental animals. This is obvious from a steady year‐to‐year increase number publications reporting use this model. Since compilation preceding review 1998, more than 1000 new studies using conditioning have been published, aim present provide an overview these recent publications. There are trends developments that literature last decade. First, as knockout transgenic animals become available, increasingly used assess or rewards genetically modified Second, there still small but growing on aspects pain, field pre‐clinical research has so far received little attention, because lack appropriate animal models. Third, widely tolerance sensitization rewarding induced by pre‐treatment regimens. Fourth, extinction/reinstatement procedures becoming popular. interesting approach thought model certain relapse addictive behavior previously almost exclusively studied drug self‐administration paradigms. It now also established provides additional technically easy important phenomenon. The enormous covered prevented in‐depth discussion many methodological, pharmacological neurobiological aspects; large extent, presentation data had limited short condensed summary relevant findings.

Language: Английский

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Opposing Patterns of Signaling Activation in Dopamine D₁and D₂Receptor-Expressing Striatal Neurons in Response to Cocaine and Haloperidol

Journal of Neuroscience, Journal Year: 2008, Volume and Issue: 28(22), P. 5671 - 5685

Published: May 28, 2008

Psychostimulants and other drugs of abuse activate extracellular signal-regulated kinase (ERK) in the striatum, through combined stimulation dopamine D 1 receptors (D1Rs) glutamate NMDA receptors. Antipsychotic similar signaling proteins striatum by blocking 2 (D2Rs). However, neurons which these pathways are activated psychotropic not precisely identified. We used transgenic mice, enhanced green fluorescent protein (EGFP) expression was driven D1R promoter ( drd1a -EGFP) or D2R drd2 -EGFP). confirmed -EGFP striatonigral striatopallidal neurons. Drd2 also expressed cholinergic interneurons, whereas no either detected GABAergic interneurons. Acute cocaine treatment increased phosphorylation ERK its direct indirect nuclear targets, mitogen- stress-activated kinase-1 (MSK1) histone H3, exclusively D1R-expressing output dorsal nucleus accumbens. Cocaine-induced c-Fos Zif268 predominated but observed D2R-expressing One week after repeated administration, cocaine-induced responses were decreased, with exception striatum. The remained confined to In contrast, acute haloperidol injection ERK, MSK1, H3 only induced c-fos zif268 predominantly Our results demonstrate that specifically two completely segregated populations striatal neurons, providing evidence for selective mechanisms exert their long-term effects.

Language: Английский

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Decoding the Epigenetic Language of Neuronal Plasticity

Neuron, Journal Year: 2008, Volume and Issue: 60(6), P. 961 - 974

Published: Dec. 1, 2008

Language: Английский

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Epigenetic Mechanisms in Cognition

Neuron, Journal Year: 2011, Volume and Issue: 70(5), P. 813 - 829

Published: June 1, 2011

Language: Английский

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Dopamine receptors – IUPHAR Review 13

British Journal of Pharmacology, Journal Year: 2014, Volume and Issue: 172(1), P. 1 - 23

Published: Oct. 17, 2014

The variety of physiological functions controlled by dopamine in the brain and periphery is mediated D1, D2, D3, D4 D5 GPCRs. Drugs acting on receptors are significant tools for management several neuropsychiatric disorders including schizophrenia, bipolar disorder, depression Parkinson's disease. Recent investigations receptor signalling have shown that receptors, apart from their canonical action cAMP-mediated signalling, can regulate a myriad cellular responses to fine-tune expression dopamine-associated behaviours functions. Such mechanisms may involve alternate G protein coupling or non-G involving ion channels, tyrosine kinases proteins such as β-arrestins classically involved GPCR desensitization. Another level complexity growing appreciation roles played heteromers. Applications new vivo techniques significantly furthered understanding receptors. Here we provide an update current knowledge regarding complex biology, physiology pharmacology

Language: Английский

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Critical Involvement of cAMP/DARPP-32 and Extracellular Signal-Regulated Protein Kinase Signaling in L-DOPA-Induced Dyskinesia

Journal of Neuroscience, Journal Year: 2007, Volume and Issue: 27(26), P. 6995 - 7005

Published: June 27, 2007

The molecular basis of l-3,4-dihydroxyphenylalanine (l-DOPA)-induced dyskinesia (LID), one the major hindrances in current therapy for Parkinson9s disease, is still unclear. We show that attenuation cAMP signaling medium spiny neurons striatum, achieved by genetic inactivation dopamine and cAMP-regulated phosphoprotein 32 kDa (DARPP-32), reduces LID. also that, dyskinetic mice, sensitized cAMP/cAMP-dependent protein kinase/DARPP-32 leads to phosphorylation/activation extracellular signal-regulated kinases 1 2 (ERK1/2). increase ERK1/2 phosphorylation associated with results activation mitogen- stress-activated kinase-1 (MSK-1) histone H3, two downstream targets ERK involved transcriptional regulation. In line these observations, we found c-Fos expression abnormally elevated striata mice affected Persistent enhancement cascade implicated generation Thus, pharmacological using SL327 (α-[amino[(4-aminophenyl)thio]methylene]-2-(trifluoromethyl)benzeneacetonitrile), an inhibitor mitogen-activated kinase/ERK kinase, MEK, during chronic l-DOPA treatment counteracts induction dyskinesia. Together, indicate a significant proportion abnormal involuntary movements developed response are attributable hyperactivation striatal pathway including sequential DARPP-32, ERK1/2, MSK-1, H3.

Language: Английский

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Epigenetic mechanisms of drug addiction

Neuropharmacology, Journal Year: 2013, Volume and Issue: 76, P. 259 - 268

Published: April 30, 2013

Language: Английский

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Epigenetic mechanisms in drug addiction

Trends in Molecular Medicine, Journal Year: 2008, Volume and Issue: 14(8), P. 341 - 350

Published: July 17, 2008

Language: Английский

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