ACTIONS OF LONG-CHAIN ALCOHOLS ON GABA(A) AND GLUTAMATE RECEPTORS - RELATION TO IN-VIVO EFFECTS

1 The effects of n-alcohols on GABA(A) and glutamate receptor systems were examined, and in vitro effectiveness was compared with in vivo ef fects in mice and tadpoles. We expressed GABA(A), NMDA, AMPA, or kaina te receptors in Xenopus oocytes and examined the actions of n-alcohols on receptor function using two-electrode voltage clamp recording. 2 T he function of GABA(A) receptors composed of alpha(1) beta(1) or alpha (1) beta(1) gamma(2L) subunits was potentiated by all of the n-alcohol s studied (butanol-dodecanol). 3 In contrast to GABA(A) receptors, glu tamate receptors expressed from mouse cortical mRNA or from cRNAs enco ding AMPA (GluR3)- or kainate (GluR6)-selective subunits were much les s sensitive to longer chain alcohols. In general, octanol and decanol were either without effect or high concentrations were required to pro duce inhibition. 4 In contrast to the lack of behavioural effects by l ong chain alcohols reported previously, decanol produced loss of right ing reflex in short- and long-sleep mice, indicating that the in vivo effects of decanol may be due in part to actions at GABA(A) receptors. Furthermore, butanol, hexanol, octanol, and decanol produce similar p otentiation of GABA(A) receptor function at concentrations required to cause loss of righting reflex in tadpoles, an in vivo model where alc ohol distribution is not a compromising factor. 5 Thus, the in vivo ef fects of long chain alcohols are not likely to be due to their actions on NMDA, AMPA, or kainate receptors, but may be due instead to potent iation of GABA(A) receptor function.