Chronic ethanol differentially alters susceptibility to chemically inducedconvulsions in withdrawal seizure-prone and -resistant mice

Withdrawal seizure-prone (WSP) and withdrawal seizure-resistant (WSR) mice were selectively bred to have severe (WSP) or mild (WSR) handling-induced c onvulsions after chronic ethanol inhalation. The purpose of the present exp eriments was to determine whether seizure susceptibility differences betwee n WSP and WSR mice during ethanol withdrawal were specific to agents acting at gamma-aminobutyric acid(A) or excitatory amino acid (EAA) receptors. Ma le WSP and WSR mice were exposed to ethanol vapor or air for 24 or 72 h. Du ring peak withdrawal (i.e., between 6.5 and 8 h after removal from the inha lation chambers), separate groups of animals were administered pentylenetet razol, (+)bicuculline, N-methyl-D-aspartate, kainic acid, or strychnine via timed tail vein infusion. Withdrawal from ethanol significantly increased sensitivity to pentylenetetrazol and (+)bicuculline versus air-exposed WSP and WSR mice. In contrast, sensitivity to N-methyl-D-aspartate-induced conv ulsions was significantly decreased in the ethanol-exposed WSR and unchange d in the ethanol-exposed WSP mice. Sensitivity to kainic acid was significa ntly increased in both ethanol-exposed WSR and WSP mice, although the magni tude of change in sensitivity was greater in the ethanol-withdrawing WSP li ne. Interestingly, sensitivity to strychnine was decreased similarly in the ethanol-exposed WSP and WSR mice, compared with their respective air-expos ed animals. These results suggest that chronic ethanol increased sensitivit y to convulsants active at gamma-aminobutyric acid(A) receptors similarly i n WSP and WSR mice, but differentially changed sensitivity to convulsants a ctive at EAA receptors in the lines. This supports a role for EAA systems i n determining genetic susceptibility to alcohol withdrawal.