RT Journal Article
SR Electronic
T1 Interaction Between Hyperthermia and Oxygen Radical Formation in the 5-Hydroxytryptaminergic Response to a Single Methamphetamine Administration
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 281
OP 285
VO 283
IS 1
A1 Fleckenstein, Annette E.
A1 Wilkins, Diana G.
A1 Gibb, James W.
A1 Hanson, Glen R.
YR 1997
UL http://jpet.aspetjournals.org/content/283/1/281.abstract
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