ETHANOL WITHDRAWAL HYPEREXCITABILITY IN-VIVO AND IN ISOLATED MOUSE HIPPOCAMPAL SLICES

Withdrawal hyperexcitability was seen in isolated mouse hippocampal sl ices, prepared after chronic treatment with ethanol, by inhalation for 2 weeks. The pattern of hyperexcitability differed from those seen pr eviously when a different method of ethanol administration and a diffe rent strain of mice were used. Thresholds for field potentials were de creased, but the transient increase in paired pulse potentiation, repo rted earlier, was not evident. Chronic administration of the calcium c hannel antagonist, isradipine (PN-200-110) during ethanol treatment si gnificantly decreased the withdrawal syndrome, both in vivo and in vit ro. Brain concentrations of isradipine during the test period were fou nd to be sufficient to produce acute effects on the withdrawal hyperex citability. No changes were seen in the field potentials when slices w ere prepared after treatment with isradipine alone. A small, but signi ficant, increase in excitability was seen in vivo after the treatment with isradipine alone. Previous studies showed that isradipine did not protect against the hyperexcitability due to gamma-aminobutyric acid (GABA)(A) antagonism, so the results suggest that neuronal calcium cha nnels may be involved in ethanol withdrawal hyperexcitability, but dec reases in GABA(A) inhibition may not be important.