Effect of acute alcohol withdrawal on sensitivity to pro- and anticonvulsant treatments in WSP mice.
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.
Crabbe
J C
JC
Research Service Department of Veterans Affairs Medical Center, Portland, OR 97201.
Merrill
C M
CM
Belknap
J K
JK
D000430:Alcohol Withdrawal Delirium / Q000235:genetics / Q000503:physiopathology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001143:Arousal / Q000187:drug effects / Q000502:physiology; D003292:Convulsants / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006234:Handling, Psychological; D007608:Kainic Acid / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D016202:N-Methylaspartate / Q000494:pharmacology; D010433:Pentylenetetrazole / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D012640:Seizures / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology*
D000927:Anticonvulsants; D003292:Convulsants; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D003975:Diazepam; D007608:Kainic Acid; D010433:Pentylenetetrazole