Acute and chronic actions of ethanol on CA1 hippocampal responses to serotonin.
The effects of acute or chronic ethanol on serotonin (5-HT)-induced membrane hyperpolarization and inhibition of the slow Ca2(+)-dependent after hyperpolarization (sAHP) were recorded in rat CA1 pyramidal neurons in hippocampal slices using sharp intracellular electrodes. 5-HT (1-100 microM) caused concentration-dependent hyperpolarization of the membrane that was not altered by simultaneous 30 mM ethanol treatment, but blunted by 10 microM buspirone, a weak 5-HT1A agonist. 5-HT (1-30 microM) also partially inhibited (approximately 40%) the sAHP following a burst of five or more action potentials. Initially ethanol (30 mM) alone did not alter the sAHP, but over a period of 38 min, a slow increase in amplitude (approximately 40%) was observed. 5-HT-mediated inhibition of the sAHP was significantly greater with ethanol present, regardless of the length of exposure. Pyramidal neurons in hippocampal slices prepared from ethanol-dependent animals showed no obvious signs of withdrawal related hyperexcitability and neither concentration-dependent membrane hyperpolarization nor sAHP inhibition caused by 5-HT were significantly changed from responses in controls. These results suggest that hyperpolarizing responses to 5-HT in hippocampal CA1 pyramidal neurons are functionally resistant to acute or chronic ethanol treatment. 5-HT-mediated inhibition of the sAHP is enhanced by ethanol acutely, but does not show an adaptive change as a result of ethanol dependence.
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Department of Medical Pharmacology & Toxicology, Texas A & M University College of Medicine, College Station 77843-1114, USA.
Frye
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D000818:Animals; D002065:Buspirone / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004361:Drug Tolerance; D004594:Electrophysiology; D000431:Ethanol / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013997:Time Factors
D002492:Central Nervous System Depressants; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D000431:Ethanol; D002065:Buspirone