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 CAI pyramidal neurons in hippocampal slices using sharp intracellular electrodes. 5-HT (1-100 mu M) caused concentration-dependent hyperpolarization of the membrane that was not altered by simultaneous 30 mM ethanol treatment, but blunted by 10 mu M buspirone, a weak 5-HT1A agonist. 5-HT (1-30 mu M) also partially inhibited (similar to 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 (similar to 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.