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Effect of Acute Alcohol Withdrawal on Sensitivity to Pro‐and Anticonvulsant Treatments in WSP Mice
Author(s) -
Crabbe John C.,
Merrill Catherine M.,
Belknap John K.
Publication year - 1993
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1993.tb05235.x
Subject(s) - pharmacology , diazepam , anticonvulsant , ethanol , convulsant , chemistry , convulsion , kainic acid , kindling , convulsants , ratón , medicine , glutamate receptor , epilepsy , receptor , stimulation , biochemistry , psychiatry
Through the genetic technique of selective breeding, a mouse line [Withdrawal Seizure Prone (WSP)] has been developed that expresses severe handling‐induced convulsions (HIC) after cessation of chronic ethanol exposure. These mice also display rebound elevations in HIC after a single ethanol injection. In the current studies, we tested WSP mice in several paradigms. WSP mice were found to be marginally sensitive to the effects of acute doses of dizocilpine to reduce HIC. However, when tested during acute withdrawal from a single ethanol injection, WSP were more sensitive to this compound. Although N‐methyl‐ d ‐aspartate significantly elevated HIC in naive WSP mice, it was more effective at low doses when given during acute withdrawal. Withdrawing mice were slightly more sensitive than naive mice to kainic acid. Pentylenetetrazole elevated HIC in naive and withdrawing mice; it was marginally more effective in naive mice. Diazepam inhibited HIC in both naive and withdrawing mice, and was slightly more effective during acute withdrawal. This pattern of results suggests that acute alcohol withdrawal is accompanied by altered sensitivity to convulsants and anticonvulsants. These changes include enhanced sensitivity in at least two excitatory amino acid‐gated ion channel binding sites.