Effect of methamphetamine on tryptophan hydroxylase activity: role of hyperthermia

A single administration of methamphetamine (15 mg/kg, s.c.) decreased activity of the 5-hydroxytryptamine (5-HT)-synthesizing enzyme, tryptophan hydroxylase, in rat striatum 1 h after administration. Methamphetamine also increased core body temperatures by greater than 3 degrees C in these rats. Prevention of hyperthermia attenuated the methamphetamine-induced decrease in tryptophan hydroxylase activity. Core temperature at the time of injection (from 37.7 degrees C to 40 degrees C) did not influence the magnitude of this decrease. Moreover, augmenting, methamphetamine-induced hyperthermia (from approximately 41 to 42 degrees C) did not cause a further decrease in tryptophan hydroxylase activity. These data indicate that temperature contributes to, but is not solely responsible for, methamphetamine-induced 5-HT neuronal impairment.