COMPARISON OF THE EFFECTS OF DRUGS ON HYPEREXCITABILITY INDUCED IN HIPPOCAMPAL SLICES BY WITHDRAWAL FROM CHRONIC ETHANOL-CONSUMPTION

1 The effects of drugs, previously demonstrated to have a range of eff ects on the behavioural signs of ethanol withdrawal hyperexcitability, were examined in area CAl in isolated hippocampal slices prepared aft er withdrawal from chronic ethanol in vivo. 2 The decreases seen after the ethanol treatment in the thresholds for production of single and multiple population spikes were prevented when the dihydropyridine cal cium channel antagonist, isradipine, was included in the perfusion med ium at 4 mu M. 3 Another dihydropyridine, felodipine, which had no act ivity against withdrawal signs in vivo, did not affect the changes in field potentials, at concentrations up to 10 mu M. 4 Diltiazem, which increased withdrawal hyperexcitability in vivo, had no effect on the w ithdrawal changes in field potentials at 30 mu M; higher concentration s affected the control slices. 5 The novel anticonvulsant, gabapentin, at 1 mu M but not at 100 nM, significantly decreased the signs of wit hdrawal hyperexcitability in the hippocampal slices. When the CCKB ant agonist, CI988, was added to the bathing medium, at 1 mu M, there were small, but significant decreases in the withdrawal hyperexcitability. 6 The results showed that the actions of these drugs on the changes i n the field potentials in isolated hippocampal slices were very simila r to their previously demonstrated effects on the convulsive signs of ethanol withdrawal in vivo, but differences were seen in the correspon ding comparison with anxiolytic actions in vivo.