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Experimental Brain Research

, Volume 230, Issue 4, pp 477–511 | Cite as

Multiple controls exerted by 5-HT2C receptors upon basal ganglia function: from physiology to pathophysiology

  • P. De DeurwaerdèreEmail author
  • M. Lagière
  • M. Bosc
  • S. Navailles
Serotonin

Abstract

Serotonin2C (5-HT2C) receptors are expressed in the basal ganglia, a group of subcortical structures involved in the control of motor behaviour, mood and cognition. These receptors are mediating the effects of 5-HT throughout different brain areas via projections originating from midbrain raphe nuclei. A growing interest has been focusing on the function of 5-HT2C receptors in the basal ganglia because they may be involved in various diseases of basal ganglia function notably those associated with chronic impairment of dopaminergic transmission. 5-HT2C receptors act on numerous types of neurons in the basal ganglia, including dopaminergic, GABAergic, glutamatergic or cholinergic cells. Perhaps inherent to their peculiar molecular properties, the modality of controls exerted by 5-HT2C receptors over these cell populations can be phasic, tonic (dependent on the 5-HT tone) or constitutive (a spontaneous activity without the presence of the ligand). These controls are functionally organized in the basal ganglia: they are mainly localized in the input structures and preferentially distributed in the limbic/associative territories of the basal ganglia. The nature of these controls is modified in neuropsychiatric conditions such as Parkinson’s disease, tardive dyskinesia or addiction. Most of the available data indicate that the function of 5-HT2C receptor is enhanced in cases of chronic alterations of dopamine neurotransmission. The review illustrates that 5-HT2C receptors play a role in maintaining continuous controls over the basal ganglia via multiple diverse actions. We will discuss their interest for treatments aimed at ameliorating current pharmacotherapies in schizophrenia, Parkinson’s disease or drugs abuse.

Keywords

Serotonin 2C receptor Basal ganglia Dopamine Motor control Parkinson Dyskinesia Addiction 

Abbreviations

5-HT2C receptor

Serotonin2C receptor

5-HT

Serotonin

DRN

Dorsal raphe nucleus

MRN

Medial raphe nucleus

5,7-DHT

5,7-Dihydroxytryptamine

DA

Dopamine

6-OHDA

6-Hydroxydopamine

MPTP

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

CNS

Central nervous system

HFS

High-frequency stimulation

NAc

Nucleus accumbens

STN

Subthalamic nucleus

EPN

Entopeduncular nucleus

GPi

Internal globus pallidus

GPe

External globus pallidus

SNc

Substantia nigra pars compacta

SNr

Substantia nigra pars reticulata

VTA

Ventral tegmental area

OFC

Orbitofrontal cortex

mPFC

Medial prefrontal cortex

8-OH-DPAT

8-Hydroxy-2-(di-n-propylamino)tetralin

m-CPP

Metachlorophenylpiperazine

TFMPP

Trifluoromethylphenylpiperazine

DOI

1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane

DOB

2,5-Dimethoxy-4-bromoamphetamine

MK-212

2-Chloro-6-(1-piperazinyl)pyrazine

RU-29469

5-Methoxy-3-(1,2,5,6-tetrahydro-4-pyridinyl)-1H-indole

Ro 60-0175

S-2-(6-chloro-5-fluoroindol-1-yl)-1-methylethylamine

WAY-163909

(7bR,10aR)-1,2,3,4,8,9,10,10a-octahydro-7bH-cyclopenta-[b][1,4]diazepino[6,7,1hi]indole

SB 228357

1-5[-fluoro-3-(3-pyridyl)phenyl-carbamoyl]-5-methoxy-6-trifluoromethylindoline

SB 206553

5-Methyl-1-(3-pyridylcarbamoyl)-1,2,3,5-tetrahydropyrrolo[2,3-f]indole

S32006

N-Pyridin-3-yl-1,2-dihydro-3H-benzo[e]indole-3-carboxamide

SB 242084

6-Chloro-5-methyl-1-[6-(2-methylpiridin-3-yloxy)pyridine-3-yl carbamoyl] indoline

SB 243213

5-Methyl-1-[[2-[(2-methyl-3-pyridyl)oxy]-5-pyridyl]carbamoyl]-6-trifluoromethylindoline

SDZ SER-082

(+)-cis 4,5,7a,8,9,10,11,11a-octahydro-7H-10-methylindolo[1,7-bc][2,6]-naphthyridine

RS-102221

N-{5-[5-(2,4-dioxo-1,3,8-triazaspiro[4.5]dec-8-yl)pentanoyl] -2,4-dimethoxyphenyl}-4-(trifluoromethyl)benzenesulfonamide

SB-215505

(6-Chloro-5-methyl-1-(5-quinolylcarbamoyl) indoline

MDL-100907

(R-(+)-a-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol)

SB 200646

N-(1-methyl-5-indolyl)-N′-(3-pyridyl) urea

GAD

Glutamic acid decarboxylase

TH

Tyrosine hydroxylase

RT-PCR

Reverse transcription polymerase chain reaction

Q-PCR

Quantitative polymerase chain reaction

IP

Inositol phosphate

PLC

Phospholipase C

PLA2

Phospholipase A2

BOLD

Blood oxygen dependent level

fMRI

Functional magnetic resonance imaging

OCD

Obsessive compulsive disorders

ICD

Impulse control disorders

5-CSRTT

5-Choice serial reaction time task

EPS

Extrapyramidal side effects

Notes

Acknowledgments

This work was supported by grants from Centre National de la Recherche Scientifique, Bordeaux University and the European Cooperation in Science and Technology (COST action CM1103). Mélanie Lagière is a fellowship recipient from the Ministère de la Recherche et de l’Enseignement Supérieur. We are grateful to Pr Marie-Françoise Chesselet and Dr Laurence Mignon for discussions about some parts of the manuscript.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • P. De Deurwaerdère
    • 1
    • 2
    Email author
  • M. Lagière
    • 1
    • 2
  • M. Bosc
    • 1
    • 2
  • S. Navailles
    • 1
    • 2
  1. 1.Université de BordeauxBordeaux CedexFrance
  2. 2.Centre National de la Recherche Scientifique (Unité Mixte de Recherche 5293)Université Bordeaux SegalenBordeaux CedexFrance

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