Alcohol effects on gamma-aminobutyric acid type A receptors: are extrasynaptic receptors the answer?

GABA(A) receptors have long been implicated in mediating at least part of the actions of ethanol in mammalian brain. However, until very recently, reports of the actions of EtOH on recombinant receptors have required very high doses of ethanol and animals lacking receptor subunits shown to be important for ethanol actions in vitro did not support the view that these subunits are crucial in ethanol actions. Recombinant alpha4beta3delta and alpha6beta3delta GABA(A) receptors are uniquely sensitive to ethanol, with a dose-response relationship mirroring the well known effects of alcohol consumption on the human brain. Receptors containing the delta subunit are thought to be located extrasynaptically and it will be important to determine if these extrasynaptic GABA(A) receptor subunit combinations mediate low dose alcohol effects in vivo.