GABAA receptor modulation of 5-HT neuronal firing in the median raphe nucleus:: Implications for the action of anxiolytics

5-HT neurones in the median raphe nucleus (MRN) are involved in anxiety and the steep/wake cycle. Here, using in vitro electrophysiology, we examined if the firing of MRN 5-HT neurones is regulated by GABAA receptors. The GABA(A) receptor agonists THIP and muscimol caused concentration dependent inhibition of MRN 5-HT neurones. The GABA(A) receptor antagonist bicuculline blocked the responses to THIP and muscimol. Bicucuttine atone increased the basal firing activity. Responses to THIP were enhanced by the Z hypnotic zolpidem at concentrations selective for the alpha 2/alpha 3 subunits of the GABA(A) receptor (0.2 and 1 mu M) but not at a concentration selective for the a, subunit (0.02 mu M). Consistent with these functional data, 5-HT neurones have been shown to express the alpha(3) (but not alpha(2)) subunit. The anxiolytic effects of GABAA receptor modulators are reportedly mediated by alpha(3)-containing receptors. Hence the MRN 5-HT system may be a target for anxiolytic drugs. (c) 2006 Elsevier B.V. and ECNP. All rights reserved.