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5-HT2A Receptors in the Basal Ganglia

  • Cristina Miguelez
  • Teresa Morera-Herreras
  • Philippe De Deurwaerdère
Chapter
Part of the The Receptors book series (REC, volume 32)

Abstract

The serotonin2A (5-HT2A) receptor is present in the basal ganglia (BG), a group of subcortical structures involved in the control of motor behaviours. It is one of the numerous serotonin (5-HT) G-protein coupled receptors responding to the release of 5-HT from neurons of the dorsal raphe nucleus. The interest brought to the function of 5-HT2A receptors in the BG is related to the possible implication of 5-HT2 receptors in the regulation of mesencephalic dopaminergic neurons and the deleterious side effects of long-term treatment with antipsychotic medication.

The 5-HT2A receptors are mostly expressed in the cortex and to a lesser extent in the BG, where other 5-HT receptor subtypes show stronger expression. Nonetheless, numerous cells including dopaminergic, GABAergic, glutamatergic or cholinergic neurons express 5-HT2A receptors brain-wide. Correspondingly, 5-HT2A receptors modulate the metabolic and electrophysiological activity of some neuronal populations including dopaminergic and GABAergic neurons. This control involves 5-HT2A receptors in the BG and is specific and state-dependent, in particular with regard to the level of dopaminergic transmission. Behavioural data have also shown that 5-HT2A receptor agents modulate the effects of a variety of psychotropic agents including drugs of abuse and antipsychotic drugs. Moreover, the 5-HT2A receptor-mediated modulation is altered in animal models of Parkinson’s disease, tardive dyskinesia, L-DOPA-induced dyskinesia and drug addiction.

This chapter summarizes data exploring the role of 5-HT2A receptors in the BG, which remains an important topic for research aimed at ameliorating current treatments of schizophrenia, Parkinson’s disease and addiction.

Keywords

Striatum Cortex Substantia Nigra Serotonin Dopamine Drug of Abuse Electrophysiology Behaviour Intracerebral Microdialysis Pharmacology 

Abbreviations

5-HT

Serotonin

5-HT2A receptor

Serotonin 2A receptor subtype

6-OHDA

6-Hydroxydopamine

BG

Basal Ganglia

DA

Dopamine

DOI

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

DRN

Dorsal raphe nucleus

EP

Entopeduncular nucleus

EPS

Extrapyramidal side effects

GPe

External globus pallidus

GPi

Internal globus pallidus

IHC

Immunohistochemical studies

LSD

Lysergic acid diethylamide

m-CPP

Metachlorophenylpiperazine

MDL 100,907

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

MPTP

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

MRN

Medial raphe nucleus

mRNA ISH

mRNA in situ hybridization

NAc

Nucleus Accumbens

OCD

Obsessive Compulsive Disorders

PCP

Phencyclidine

pCPA

para-chlorophenylalanine

PD

Parkinson’s disease

PET

Positron emission tomography

PPE

Preproenkephalin

PPT

Preprotachykinin

Ro 60–0175

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

RT-PCR

Reverse transcription polymerase chain reaction

RU-29469

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

SB 228357

1–5[−fluoro-3-(3-pyridyl)phenyl-carbamoyl] -5- methoxy-6-trifluo-romethylindoline

SNc

Substantia nigra pars compacta

SNr

Substantia nigra pars reticulata

SPNs

Spiny projecting neurons

STN

Subthalamic nucleus

TFMPP

Trifluoromethylphenylpiperazine

TH

Tyrosine hydroxylase

VTA

Ventral tegmental area

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Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Cristina Miguelez
    • 1
  • Teresa Morera-Herreras
    • 1
  • Philippe De Deurwaerdère
    • 2
    • 3
  1. 1.Department of Pharmacology, Faculty of Medicine and NursingUniversity of the Basque Country (UPV/EHU)LeioaSpain
  2. 2.Université de BordeauxBordeauxFrance
  3. 3.Centre National de la Recherche Scientifique, UMR 5287BordeauxFrance

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