Elevated prodynorphin expression associated with ethanol withdrawal convulsions

The hypothesis that kappa-opioid system activity may in part mediate convul sions exhibited during ethanol withdrawal was tested by exposing Withdrawal Seizure-Prone (WSP) and Withdrawal Seizure-Resistant (WSR) mice to chronic ethanol. Whole brain was harvested for RNA isolation and prodynorphin mRNA steady-state levels in whole brain were examined using Northern blot analy sis. The data revealed significantly increased levels of prodynorphin mRNA expression in mice susceptible to ethanol withdrawal convulsions after with drawal, with no corresponding increase in prodynorphin steady-state levels in mice resistant to ethanol withdrawal convulsions. These findings were no t due to basal differences in prodynorphin expression between the WSP and W SR mice. To verify that the differences observed were not due to an ethanol -induced global alteration in gene transcription, mRNA levels of the housek eeping gene glyceraldehyde-3-phosphate dehydrogenase were measured. Glycera ldchyde-3-phosphate dehydrogenase expression was unchanged following both c hronic exposure to ethanol and chronic exposure followed by withdrawal. The se results extend our understanding of prodynorphin's role in generalized s eizure activity to include ethanol withdrawal-induced convulsions. Our find ings suggest that prodynorphin expression is modulated during ethanol withd rawal convulsions, or alternatively, prodynorphin may mediate the severity of ethanol withdrawal convulsions. (C) 2000 Elsevier Science Ltd. All right s reserved.