Brain region-dependent sensitivity of GABAA receptor-mediated responses to modulation by ethanol.
Simultaneous extracellular and intracellular electrophysiological recordings were made from the CA1 region of rat hippocampal brain slices during superfusion with ethanol. Ethanol (80 mM) had a biphasic effect on the extracellularly recorded population spike, with an initial increase followed by a significant reduction (38%) in this response, which was maximal 10 to 15 min after the start of ethanol application. Concurrent intracellular recordings in the CA1 showed a small (0.7 mV) hyperpolarization of the resting membrane potential, with no significant change in the input impedance, EPSP, GABAA and GABAB IPSPs, or after hyperpolarization (AHP) following depolarizing current injection. Ethanol reduced the amplitude and duration of depolarizing responses to brief, localized pressure-ejection of N-methyl-D-aspartate (NMDA) onto pyramidal neuron dendrites, but did not affect the GABAA receptor-mediated depolarizing responses to the dendritic application of GABA. In parallel studies, the effect of ethanol on GABA-stimulated 36Cl- flux was measured in microsac preparations from rat hippocampus, cerebellum, and cerebral cortex. Ethanol application caused substantial enhancement of the chloride uptake from cerebellar and cerebral cortical microsacs, but had no effect on 36Cl- influx in hippocampal microsacs. These results suggest that there are important brain region-dependent differences in the sensitivity of the GABAA receptor/chloride channel to modulation by ethanol.
Proctor
W R
WR
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262.
Allan
A M
AM
Dunwiddie
T V
TV
D000818:Animals; D002531:Cerebellum / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects; D018118:Chloride Channels; D002712:Chlorides / Q000378:metabolism; D046508:Culture Techniques; D000431:Ethanol / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008565:Membrane Proteins / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*
D018118:Chloride Channels; D002712:Chlorides; D008565:Membrane Proteins; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol