Sensitivity of postsynaptic GABAB receptors on hippocampal CA1 and CA3 pyramidal neurons to ethanol.
Baclofen-induced hyperpolarization of hippocampal CA1 and CA3 pyramidal neurons was examined to assess the impact of ethanol on postsynaptic GABAB receptors. These receptors activate outward K+ currents via a pertussis toxin-sensitive G protein cascade to reduce membrane potential during the slow inhibitory postsynaptic potential. This inhibitory action may play a role in ethanol intoxication and withdrawal excitability. In both types of pyramidal neurons, baclofen applied consecutively in increasing concentrations caused concentration dependent hyperpolarization. There were no significant differences in resting membrane potential, input resistance, maximum baclofen-induced hyperpolarization or EC50 between CA1 and CA3 neurons, although slope values were significantly smaller in the former neurons. These parameters were not significantly changed in the presence of ethanol 10-100 mM. Chronic ethanol treatment (12 days) sufficient to induce physical dependence also did not shift sensitivity or maximum response to baclofen in CA1 neurons. These results suggest that GABAB receptors in this model are essentially insensitive to ethanol and do not confirm our earlier preliminary observation of a possible down-regulation of postsynaptic GABAB receptor function by chronic ethanol treatment.
Department of Medical Pharmacology and Toxicology, Texas A & M University, College of Medicine, Station 77843-1114, USA. gdfrye@tamu.edu
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D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D004594:Electrophysiology; D000431:Ethanol / Q000494:pharmacology*; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000187:drug effects* / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D013997:Time Factors
D018080:Receptors, GABA-B; D000431:Ethanol; D001418:Baclofen