Role of brain tyrosine availability in mediating differences in ethanol sensitivity in long-sleep and short-sleep mice

TA French, KL Clay and N Weiner

Department of Pharmacology, University of Colorado School of Medicine, Denver.

Long-sleep (LS) and short-sleep (SS) mice, bred for differences in initial sensitivity to ethanol, were found to differ considerably in the effect of ethanol on brain tyrosine levels. Brain tyrosine levels are decreased in both lines of mice over a 120-min period after ethanol, but the onset of the decrease occurs earlier (15 min vs. 60 min) and the extent of the decrease is greater (39% vs. 18%) in LS mice. This phenomenon is apparently related to the greater central nervous system ethanol sensitivity of LS mice, inasmuch as prior administration of tyrosine will prevent the ethanol-induced decrease in brain tyrosine levels and result in a decrease in the ethanol-induced sleep times of LS mice. An earlier study suggested a relationship between decreased catecholamine turnover in certain brain regions of LS mice and their greater ethanol sensitivity. The present observation that tyrosine pretreatment prevents or attenuates these ethanol-induced decreases in catecholamine turnover, while ethanol sensitivity is reduced, provides additional support for this apparent relationship. If the mice are pretreated with agents (large neutral amino acids) that lower brain tyrosine, the ethanol sensitivity (sleep times) increases in both lines of mice. The increased sensitivity is associated with marked decreases in brain region catecholamine turnover in both the LS and SS mice. These results are consistent with a role for catecholamine neuronal systems in mediating some of the intoxicating actions of ethanol, in general, and the differences in LS/SS ethanol sensitivity in particular.

Volume 250, Issue 2, pp. 556-564, 08/01/1989
Copyright © 1989 by American Society for Pharmacology and Experimental Therapeutics