Effect of genetic and pharmacological blockade of GABA receptors on the 5-HT2C receptor function during stress

Cédric B.P. Martin, Martin Gassmann, Caroline Chevarin, Michel Hamon, Uwe Rudolph, Bernhard Bettler, Laurence Lanfumey, Raymond Mongeau

Research output: Contribution to journalArticlepeer-review

Abstract

Serotonin (5-HT)2C receptors play a role in psychoaffective disorders and often contribute to the antidepressant and anxiolytic effects of psychotropic drugs. During stress, activation of these receptors exerts a negative feedback on 5-HT release, probably by increasing the activity of GABAergic interneurons. However, to date, the GABA receptor types that mediate the 5-HT2C receptor-induced feedback inhibition are still unknown. To address this question, we assessed the inhibition of 5-HT turnover by a 5-HT2C receptor agonist (RO 60-0175) at the hippocampal level and under conditions of stress, after pharmacological or genetic inactivation of either GABA-A or GABA-B receptors in mice. Neither the GABA-B receptor antagonist phaclofen nor the specific genetic ablation of either GABA-B1a or GABA-B1b subunits altered the inhibitory effect of RO 60-0175, although 5-HT turnover was markedly decreased in GABA-B1a knock-out mice in both basal and stress conditions. In contrast, the 5-HT2C receptormediated inhibition of 5-HT turnover was reduced by the GABA-A receptor antagonist bicuculline. However, a significant effect of 5-HT2C receptor activation persisted in mutant mice deficient in the α3 subunit of GABA-A receptors. It can be inferred that non-α3 subunit-containing GABA-A receptors, but not GABA-B receptors, mediate the 5-HT2C-induced inhibition of stress-induced increase in hippocampal 5-HT turnover in mice.

Original languageEnglish (US)
Pages (from-to)566-572
Number of pages7
JournalJournal of Neurochemistry
Volume131
Issue number5
DOIs
StatePublished - Dec 2014

Keywords

  • Bicuculline
  • GABA-A α3 subunit
  • GABA-B
  • Knockout
  • Phaclofen

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Effect of genetic and pharmacological blockade of GABA receptors on the 5-HT<sub>2C</sub> receptor function during stress'. Together they form a unique fingerprint.

Cite this