GABA(A) receptor modulation of 5-HT neuronal firing in the median raphe nucleus: implications for the action of anxiolytics.

摘要

5-HT neurones in the median raphe nucleus (MRN) are involved in anxiety and the sleep/wake cycle. Here, using in vitro electrophysiology, we examined if the firing of MRN 5-HT neurones is regulated by GABA(A) 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. Bicuculline alone 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 1microM) but not at a concentration selective for the alpha(1) subunit (0.02microM). 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 GABA(A) receptor modulators are reportedly mediated by alpha(3)-containing receptors. Hence the MRN 5-HT system may be a target for anxiolytic drugs.