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

Neuropharmacology. 2010 Jun;58(8):1220-7. doi: 10.1016/j.neuropharm.2010.03.003. Epub 2010 Mar 11.


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).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Action Potentials
  • Animals
  • Brain Stem / cytology
  • Brain Stem / drug effects
  • Brain Stem / physiology
  • GABA Agonists / pharmacology*
  • GABA Uptake Inhibitors
  • In Vitro Techniques
  • Inhibitory Postsynaptic Potentials
  • Male
  • Miniature Postsynaptic Potentials
  • Motor Neurons / drug effects*
  • Motor Neurons / physiology
  • Muscimol / pharmacology
  • Nipecotic Acids / pharmacology
  • Patch-Clamp Techniques
  • Pyridines / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA-A / physiology*
  • Vagus Nerve / drug effects*
  • Vagus Nerve / physiology
  • Zolpidem
  • gamma-Aminobutyric Acid / physiology*


  • GABA Agonists
  • GABA Uptake Inhibitors
  • Nipecotic Acids
  • Pyridines
  • Receptors, GABA-A
  • nipecotic acid
  • Muscimol
  • gamma-Aminobutyric Acid
  • Zolpidem