Role of GABAA receptors in the physiology and pharmacology of sleep
- 5 May 2009
- journal article
- review article
- Published by Wiley in European Journal of Neuroscience
- Vol. 29 (9), 1779-1794
- https://doi.org/10.1111/j.1460-9568.2009.06716.x
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.Keywords
This publication has 179 references indexed in Scilit:
- Acting locally but sensing globally: impact of GABAergic synaptic plasticity on phasic and tonic inhibition in the thalamusJournal Of Physiology-London, 2008
- GABAAR Plasticity during Pregnancy: Relevance to Postpartum DepressionNeuron, 2008
- Normal sleep homeostasis and lack of epilepsy phenotype in GABAA receptor α3 subunit-knockout miceNeuroscience, 2008
- From synapse to behavior: rapid modulation of defined neuronal types with engineered GABAA receptorsNature Neuroscience, 2007
- Synaptic and nonsynaptic localization of GABAA receptors containing the α5 subunit in the rat brainJournal of Comparative Neurology, 2006
- Variations on an inhibitory theme: phasic and tonic activation of GABAA receptorsNature Reviews Neuroscience, 2005
- Genetic manipulations of GABAA receptor in mice make inhibition excitingPharmacology & Therapeutics, 2004
- Abolition of zolpidem sensitivity in mice with a point mutation in the GABAA receptor γ2 subunitNeuropharmacology, 2004
- Specific γ‐hydroxybutyrate‐binding sites but loss of pharmacological effects of γ‐hydroxybutyrate in GABAB(1)‐deficient miceEuropean Journal of Neuroscience, 2003
- Effects of GABA-ergic agents on spontaneous non-convulsive epilepsy, EEG and behaviour, in the WAG/Rij inbred strain of ratsLife Sciences, 1989