Interaction between hyperthermia and oxygen radical formation in the 5-hydroxytryptaminergic response to a single methamphetamine administration.
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.
Fleckenstein
A E
AE
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City 84112, USA.
Wilkins
D G
DG
Gibb
J W
JW
Hanson
G R
GR
D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D005609:Free Radicals; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012701:Serotonin / Q000096:biosynthesis*; D014365:Tryptophan Hydroxylase / Q000378:metabolism
D005609:Free Radicals; D017382:Reactive Oxygen Species; D012701:Serotonin; D008694:Methamphetamine; D014365:Tryptophan Hydroxylase