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 sleep/wake cycle. Here, using in vitro electrophysiology, we examined if the firing of MRN 5-HT neurones is regulated by GABAA receptors. The GABAA receptor agonists THIP and muscimol caused concentration dependent inhibition of MRN 5-HT neurones. The GABAA 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 α2/α3 subunits of the GABAA receptor (0.2 and 1 μM) but not at a concentration selective for the α1 subunit (0.02 μM). Consistent with these functional data, 5-HT neurones have been shown to express the α3 (but not α2) subunit. The anxiolytic effects of GABAA receptor modulators are reportedly mediated by α3-containing receptors. Hence the MRN 5-HT system may be a target for anxiolytic drugs.