Actions of long chain alcohols on GABAA and glutamate receptors: relation to in vivo effects.
1. The effects of n-alcohols on GABAA and glutamate receptor systems were examined, and in vitro effectiveness was compared with in vivo effects in mice and tadpoles. We expressed GABAA, NMDA, AMPA, or kainate receptors in Xenopus oocytes and examined the actions of n-alcohols on receptor function using two-electrode voltage clamp recording. 2. The function of GABAA receptors composed of alpha 1 beta 1 or alpha 1 beta 1 gamma 2L subunits was potentiated by all of the n-alcohols studied (butanol-dodecanol). 3. In contrast to GABAA receptors, glutamate receptors expressed from mouse cortical mRNA or from cRNAs encoding AMPA (GluR3)- or kainate (GluR6)-selective subunits were much less sensitive to longer chain alcohols. In general, octanol and decanol were either without effect or high concentrations were required to produce inhibition. 4. In contrast to the lack of behavioural effects by long chain alcohols reported previously, decanol produced loss of righting reflex in short- and long-sleep mice, indicating that the in vivo effects of decanol may be due in part to actions at GABAA receptors. Furthermore, butanol, hexanol, octanol, and decanol produce similar potentiation of GABAA receptor function at concentrations required to cause loss of righting reflex in tadpoles, an in vivo model where alcohol distribution is not a compromising factor. 5. Thus, the in vivo effects 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 potentiation of GABAA receptor function.
Dildy-Mayfield
J E
JE
Dept. of Pharmacology, University of Colorado Health Sciences Center, Denver 80262, USA.
Mihic
S J
SJ
Liu
Y
Y
Deitrich
R A
RA
Harris
R A
RA
D000438:Alcohols / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D006801:Humans; D007608:Kainic Acid / Q000494:pharmacology; D051379:Mice; D016202:N-Methylaspartate / Q000494:pharmacology; D012333:RNA, Messenger / Q000008:administration & dosage; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000235:genetics; D017470:Receptors, Glutamate / Q000187:drug effects* / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics; D014981:Xenopus
D000438:Alcohols; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D017470:Receptors, Glutamate; D011994:Recombinant Proteins; D016202:N-Methylaspartate; D007608:Kainic Acid