Comparison of effect of ethanol on N-methyl-D-aspartate- and GABA-gated currents from acutely dissociated neurons: absence of regional differences in sensitivity to ethanol.
In vivo, ethanol alters the effect of N-methyl-D-aspartate (NMDA) and GABA in some brain regions but is without effect in others. To determine whether these regional differences were due to differences in the effect of ethanol on postsynaptic NMDA or GABAA receptors, we examined the effect of ethanol on NMDA- and GABA-gated currents from neurons acutely dissociated from the lateral septal nucleus, substantia nigra, thalamus, hippocampus, and cerebellum. Ethanol decreased the effect of NMDA similarly in all brain areas tested and had similar effects on Chinese hamster ovary cells expressing NR2A or NR2B subunits with an NR1-1a subunit. However, ifenprodil reduced the inhibition by ethanol of NMDA-gated currents from neurons isolated from the lateral septum without affecting neurons from the substantia nigra. In contrast to the robust effect of ethanol on NMDA-gated currents, ethanol (25-300 mM) was without effect on GABA-gated currents at all brain sites tested or on Ltk- cells stably expressing the alpha1, beta2, and gamma2L or gamma2S subunits. The neuroactive steroid alphaxalone profoundly enhanced GABA-gated currents in all brain areas and cell types tested, indicating a similar sensitivity to allosteric modulation; however, there was no interaction of alphaxalone with ethanol at any site tested. These data suggest that the regional differences in the effect of ethanol observed in vivo are not due to a differential action of ethanol at the postsynaptic NMDA or GABAA receptor subtypes.
Criswell
Hugh E
HE
Bowles Center for Alcohol Studies, Chapel Hill, North Carolina 27599-7178, USA. hec@med.unc.edu
Ming
Zhen
Z
Griffith
Benjamin L
BL
Breese
George R
GR
D000777:Anesthetics / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000166:cytology; D001923:Brain Chemistry / Q000187:drug effects*; D016466:CHO Cells; D002460:Cell Line; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D006224:Cricetinae; D004594:Electrophysiology; D000431:Ethanol / Q000494:pharmacology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D015640:Ion Channel Gating / Q000187:drug effects*; D016202:N-Methylaspartate / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology; D011277:Pregnanediones / Q000494:pharmacology; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D000777:Anesthetics; D002492:Central Nervous System Depressants; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D010880:Piperidines; D011277:Pregnanediones; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; C006477:alphaxalone; C010739:ifenprodil