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5-HT2A Receptors in the Central Nervous System pp 3–29Cite as

Pharmacological Analysis in Favour of a Physiological Role for the Constitutive Activity of 5-HT2A Receptors in Learning

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Part of the book series: The Receptors ((REC,volume 32))

Abstract

The Serotonin2A (5-hydroxytryptamin, 5-HT2A) receptor is one of the numerous seven transmembrane G protein coupled receptors for serotonin (5-HT) originally described as displaying a low affinity for its endogenous ligand. It is densely expressed in the cortex and the hippocampus of rodents, primates and humans brain. A role of 5-HT2A receptors in learning and memory has been proposed for years. In some behavioural tasks in rodents, 5-HT2A receptors would display a constitutive activity, a spontaneous activity of the receptor occurring without the presence of the endogenous ligand and silenced by inverse agonists. Nonetheless, the demonstration of the existence of such a subtle activity in living organisms relies on specific criteria and on clear-cut pharmacological evaluation. While it has been claimed that 5-HT2A receptor constitutive activity participates in the conditioned eyeblink response in rabbits, such an activity would not be systematically observed in other models of learning and conditioning such as the conditioned avoidance response in rats. Here, we propose a thorough pharmacological analysis of the available data arguing in favour of the involvement of constitutive activity of 5-HT2A receptors, mostly in learning tasks and discuss the functional significance of such an activity.

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Abbreviations

5,7-DHT:

5,7-dihydroxytryptamin

5-HT:

Serotonin

5-HT2A receptor:

5-hydroxytryptamine2A receptor

5-HT2C receptor:

5-hydroxytryptamine2C receptor

BOL:

d-bromolysergic acid diethylamide

CAR:

Conditioned avoidance response

CHO:

Chinese hamster ovary

DA:

dopamine

DOI:

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

DOM:

d,l-2,5-dimethoxy-4-methylamphetamine

GPCR:

G-Protein coupled receptor

HEK-293:

Human embryonic kidney 293

IP:

Inositol phosphate

LSD:

d-lysergic acid diethylamide

MDA:

d,l-methylenedioxyamphetamine

MDMA:

d,l-methylenedioxymethamphetamine

PLA2:

Phospholipase A2

PLC:

Phospholipase C

PLD:

Phospholipase D

SERT:

Serotonin transporter

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Acknowledgments

The authors are indebted to the EU COST Action CM1103 “Structure-based drug design for diagnosis and treatment of neurological diseases: dissecting and modulating complex function in the monoaminergic systems of the brain” for supporting their international collaboration.

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Authors and Affiliations

  1. Université de Bordeaux, Bordeaux, France

    Philippe De Deurwaerdère & Guillaume Drutel

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

    Philippe De Deurwaerdère

  3. Institut National de la Santé et de la Recherche Médicale, U 1215, Bordeaux, France

    Guillaume Drutel

  4. Neuroscience Division, School of Bioscience, Cardiff University, Cardiff, UK

    Giuseppe Di Giovanni

  5. Department of Physiology and Biochemistry, University of Malta, Msida, Malta

    Giuseppe Di Giovanni

Authors
  1. Philippe De Deurwaerdère
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  2. Guillaume Drutel
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  3. Giuseppe Di Giovanni
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Correspondence to Philippe De Deurwaerdère .

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Editors and Affiliations

  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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De Deurwaerdère, P., Drutel, G., Di Giovanni, G. (2018). Pharmacological Analysis in Favour of a Physiological Role for the Constitutive Activity of 5-HT2A Receptors in Learning. 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_1

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