Role of GABAA receptors in the physiology and pharmacology of sleep

Eur J Neurosci. 2009 May;29(9):1779-94. doi: 10.1111/j.1460-9568.2009.06716.x. Epub 2009 Apr 27.

Abstract

Most sedative-hypnotics used in insomnia treatment target the gamma-aminobutyric acid (GABA)(A) receptors. A vast repertoire of GABA(A) receptor subtypes has been identified and displays specific electrophysiological and functional properties. GABA(A)-mediated inhibition traditionally refers to 'phasic' inhibition, arising from synaptic GABA(A) receptors which transiently inhibit neurons. However, there is growing evidence that peri- or extra-synaptic GABA(A) receptors are continuously activated by low GABA concentrations and mediate a 'tonic' conductance. This slower type of signaling appears to play a key role in controlling cell excitability. This review aims at summarizing recent knowledge on GABA transmission, including the emergence of tonic conductance, and highlighting the importance of GABA(A) receptor heterogeneity. The mechanism of action of sedative-hypnotic drugs and their effects on sleep and the electroencephalogram will be reported. Furthermore, studies using genetically engineered mice will be emphasized, providing insights into the role of GABA(A) receptors in mechanisms underlying physiological and pharmacological sleep. Finally, we will address the potential of GABA(A) receptor pharmacology for the treatment of insomnia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Brain / drug effects*
  • Brain / physiology*
  • Humans
  • Hypnotics and Sedatives / pharmacology
  • Neural Pathways / drug effects
  • Neural Pathways / physiology
  • Neurons / drug effects
  • Neurons / physiology
  • Receptors, GABA-A / metabolism*
  • Sleep / drug effects*
  • Sleep / physiology*
  • Sleep Initiation and Maintenance Disorders / drug therapy
  • Synapses / drug effects
  • Synapses / physiology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology

Substances

  • Hypnotics and Sedatives
  • Receptors, GABA-A