PT - JOURNAL ARTICLE AU - Annette E. Fleckenstein AU - Diana G. Wilkins AU - James W. Gibb AU - Glen R. Hanson TI - Interaction Between Hyperthermia and Oxygen Radical Formation in the 5-Hydroxytryptaminergic Response to a Single Methamphetamine Administration DP - 1997 Oct 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 281--285 VI - 283 IP - 1 4099 - http://jpet.aspetjournals.org/content/283/1/281.short 4100 - http://jpet.aspetjournals.org/content/283/1/281.full SO - J Pharmacol Exp Ther1997 Oct 01; 283 AB - 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. The American Society for Pharmacology and Experimental Therapeutics