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Vol. 283, Issue 1, 281-285, 1997

Interaction Between Hyperthermia and Oxygen Radical Formation in the 5-Hydroxytryptaminergic Response to a Single Methamphetamine Administration1

Annette E. Fleckenstein, Diana G. Wilkins, James W. Gibb and Glen R. Hanson

Department of Pharmacology and Toxicology (A.E.F., J.W.G., G.R.H) and Center for Human Toxicology (D.G.W.), University of Utah, Salt Lake City, Utah

Administration of a single high dose of methamphetamine (METH) causes a rapid and reversible decrease in the activity of the tryptophan hydroxylase (TPH), the rate-limiting enzyme in the synthesis of 5-hydroxytryptamine. This effect can be reversed completely by exposing the METH-impaired enzyme to a reducing environment, which suggests that the decrease in TPH activity is a reversible oxidative consequence of free radical formation. Consistent with this hypothesis, a single METH administration to male rats increased oxygen radical formation, as demonstrated by increased striatal dihydroxybenzoic acid formation after coadministration of salicylate with METH. Prevention of METH-induced hyperthermia attenuated both the increase in dihydroxybenzoic acid formation and the decrease in TPH activity observed 1 h after METH administration. These data suggest that both reactive oxygen species and hyperthermia contribute to the acute decrease in TPH activity which results from a single METH administration.

Copyright © by The American Society for Pharmacology and Experimental Therapeutics


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