Zolpidem modulation of phasic and tonic GABA currents in the rat dorsal motor nucleus of the vagus

Hong Gao, Bret N. Smith

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Zolpidem is a widely prescribed sleep aid with relative selectivity for GABAA receptors containing α1-3 subunits. We examined the effects of zolpidem on the inhibitory currents mediated by GABAA 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 GABAA receptor-mediated tonic current (Itonic) 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 α1-3 subunits are expressed in synaptic GABAA receptors on DMV neurons. The baseline tonic GABA current is likely not mediated by these same low affinity, zolpidem-sensitive GABAA receptors. However, when the extracellular GABA concentration is increased, zolpidem-sensitive extrasynaptic GABAA receptors containing α1-3 subunits contribute to the Itonic.

Original languageEnglish
Pages (from-to)1220-1227
Number of pages8
JournalNeuropharmacology
Volume58
Issue number8
DOIs
StatePublished - Jun 2010

Bibliographical note

Funding Information:
Supported by grants from NSF IOB-0518209 and NIH ( DK056132 ).

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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