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5-HT2A Receptors in the Basal Ganglia

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Book cover 5-HT2A Receptors in the Central Nervous System

Part of the book series: The Receptors ((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.

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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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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Spain

    Cristina Miguelez & Teresa Morera-Herreras

  2. Université de Bordeaux, Bordeaux, France

    Philippe De Deurwaerdère

  3. Centre National de la Recherche Scientifique, UMR 5287, Bordeaux, France

    Philippe De Deurwaerdère

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  1. Cristina Miguelez
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  2. Teresa Morera-Herreras
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  3. Philippe De Deurwaerdère
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Correspondence to Philippe De Deurwaerdère .

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  1. Faculté de Pharmacie, Université Paris Sud, Université Paris-Saclay, Chatenay-Malabry, France

    Bruno P. Guiard

  2. Department of Physiology and Biochemistry, University of Malta, Msida MSD, Malta

    Giuseppe Di Giovanni

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Miguelez, C., Morera-Herreras, T., De Deurwaerdère, P. (2018). 5-HT2A Receptors in the Basal Ganglia. In: Guiard, B., Di Giovanni, G. (eds) 5-HT2A Receptors in the Central Nervous System. The Receptors, vol 32. Humana Press, Cham. https://doi.org/10.1007/978-3-319-70474-6_12

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