The 5-HT2C receptor subtype controls central dopaminergic systems : evidence from electrophysiological and neurochemical studies

Abstract

Several studies have focused on the role of serotonergic 5-HT2C receptors in the regulation of forebrain dopamine (DA) function and have highlighted their potential as a target for improved treatments of neuropsychiatric disorders related to central dopaminergic neuron dysfunction. This chapter was undertaken to summarize the authors’ and others’ works that have extensively explored the role of 5-HT2C receptors in the control of DA systems both in basal and drug-induced conditions, using in vivo electrophysiological and microdialytic techniques. It is well established that this receptor subtype exerts both tonic and phasic modulation of central dopaminergic function. This evidence has led to the suggestion that drugs acting on 5-HT2C receptors have potential as novel antipsychotic (APD) and antidepressant agents and may be used in the treatment of other neuropsychiatric disorders such as Parkinson disease and psychoactive substance abuse. First, the physiology, pharmacology, and anatomical distribution of the 5-HT2C receptors in the central nervous system (CNS) are reviewed. Next, experimental data regarding the effect of 5-HT2C selective agents on the neuronal activity of DA neurons of the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc), as well as the changes of basal DA release in the striatum, nucleus accumbens, and cerebral cortex, are discussed. Finally, the potential use of 5-HT2C agents in the treatment of depression, schizophrenia, Parkinson disease, and drug abuse will be also discussed.