In:
Journal of Neurochemistry, Wiley, Vol. 131, No. 5 ( 2014-12), p. 566-572
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 GABA ergic interneurons. However, to date, the GABA receptor types that mediate the 5‐ HT 2C receptor‐induced feedback inhibition are still unknown. To address this question, we assessed the inhibition of 5‐ HT turnover by a 5‐ HT 2C 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‐ HT 2C receptor‐mediated inhibition of 5‐ HT turnover was reduced by the GABA ‐A receptor antagonist bicuculline. However, a significant effect of 5‐ HT 2C receptor activation persisted in mutant mice deficient in the α 3 subunit of GABA ‐A receptors. It can be inferred that non‐α 3 subunit‐containing GABA ‐A receptors, but not GABA ‐B receptors, mediate the 5‐ HT 2C ‐induced inhibition of stress‐induced increase in hippocampal 5‐ HT turnover in mice. image Serotonin (5‐HT 2C ) receptors expressed by GABA interneurons (2) are known to drive an indirect, GABA‐mediated, inhibitory feedback control of 5‐HT neurons, especially under stressful conditions. Using mutant mice and selective ligands, we demonstrated that this feedback control involves not only GABA‐A receptors (1) but also GABA‐B1a receptors (4), that would inhibit the stimulatory influence of cortical glutamatergic afferences (3) on GABA interneurons. Adaptations of these 5‐HT‐GABA‐glu interactions may contribute to the anxiolytic effects of chronic antidepressant treatments.
Type of Medium:
Online Resource
ISSN:
0022-3042
,
1471-4159
DOI:
10.1111/jnc.2014.131.issue-5
Language:
English
Publisher:
Wiley
Publication Date:
2014
detail.hit.zdb_id:
2020528-4
SSG:
12
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