Zolpidem is a widely prescribed sleep aid with relative selectivity for GABA(A) receptors containing alpha1-3 subunits. We examined the effects of zolpidem on the inhibitory currents mediated by GABA(A) receptors using whole-cell patch-clamp recordings from DMV neurons in transverse brainstem slices from rat. Zolpidem prolonged the decay time of mIPSCs and of muscimol-evoked whole-cell GABAergic currents, and it occasionally enhanced the amplitude of mIPSCs. The effects were blocked by flumazenil, a benzodiazepine antagonist. Zolpidem also hyperpolarized the resting membrane potential, with a concomitant decrease in input resistance and action potential firing activity in a subset of cells. Zolpidem did not clearly alter the GABA(A) receptor-mediated tonic current (I(tonic)) under baseline conditions, but after elevating extracellular GABA concentration with nipecotic acid, a non-selective GABA transporter blocker, zolpidem consistently and significantly increased the tonic GABA current. This increase was suppressed by flumazenil and gabazine. These results suggest that alpha1-3 subunits are expressed in synaptic GABA(A) receptors on DMV neurons. The baseline tonic GABA current is likely not mediated by these same low affinity, zolpidem-sensitive GABA(A) receptors. However, when the extracellular GABA concentration is increased, zolpidem-sensitive extrasynaptic GABA(A) receptors containing alpha1-3 subunits contribute to the I(tonic).
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