Genetic differences in hypothalamic-pituitary-adrenal axis responsiveness to acute ethanol and acute ethanol withdrawal.
There is a growing body of evidence suggesting that corticosteroids contribute to the increased neural excitability observed during ethanol withdrawal. In the present study, this was further investigated using mouse strains which differ in ethanol withdrawal severity. DBA/2 (DBA) mice were found to display more severe acute ethanol withdrawal seizures than C57BL/6 (C57) mice. Additionally, DBA mice showed a greater stress response than C57 mice, as measured by higher plasma concentrations of adrenocorticotropic hormone (ACTH) and corticosterone, to an acute dose of ethanol. Mimicking withdrawal plasma corticosterone levels by administering corticosterone to ethanol-naive mice resulted in increases in handling-induced convulsions in the range observed during withdrawal. There did not appear to be a strain difference in sensitivity to the excitatory effects of corticosterone. In summary, the greater stress response to ethanol by DBA mice may account, in part, for the more severe ethanol withdrawal syndrome of this strain.
Roberts
A J
AJ
Department of Medical Psychology, Oregon Health Sciences University, Portland 97201.
Crabbe
J C
JC
Keith
L D
LD
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D003345:Corticosterone / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D006234:Handling, Psychological; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D012640:Seizures / Q000503:physiopathology; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*
D000431:Ethanol; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone