BODY-TEMPERATURE EFFECT ON METHYLENEDIOXYMETHAMPHETAMINE-INDUCED ACUTE DECREASE IN TRYPTOPHAN-HYDROXYLASE ACTIVITY

Brain tryptophan hydroxylase activity decreases within 15 min after a single administration of 3,4-methylenedioxymethamphetamine. In the pre sent study, the effect of body temperature on this acute decrease of t ryptophan hydroxylase activity was examined. 2 h after a single dose o f 3,4-methylenedioxymethamphetamine (20 mg/kg, s.c.), rats exhibited h yperthermia (38.7 degrees C) or hypothermia (35.8 degrees C) when main tained at 25 degrees C or 6 degrees C, respectively. The rectal temper ature of control animals maintained at 6 degrees C was not altered. Tr yptophan hydroxylase activity measured in the hippocampus, striatum an d frontal cortex of hyperthermic rats treated with 3,4-methylenedioxym ethamphetamine was decreased to 61%, 65%, and 71% of control levels, r espectively, 2 h after drug treatment. However, in hypothermic rats, 3 ,4-methylenedioxymethamphetamine had no effect on tryptophan hydroxyla se activity in the hippocampus, striatum or frontal cortex. Non-drug-i nduced hyperthermia or hypothermia did not affect tryptophan hydroxyla se activity. Since hypothermia may prevent the 3,4-methylenedioxymetha mphetamine-induced decrease in tryptophan hydroxylase activity by redu cing the formation of free radicals, the effect of a free radical scav enging agent, N-tert-butyl-alpha-phenylnitrone, was examined. N-tert-b utyl-alpha-phenylnitrone (200 mg/kg, i.p.) alone caused hypothermia bu t had no direct effect on tryptophan hydroxylase activity. Preadminist ration of N-tert-butyl-alpha-phenylnitrone prevented 3,4-methylenediox ymethamphetamine from raising the temperature above normal and attenua ted the drug-induced decrease in tryptophan hydroxylase activity in hi ppocampus, striatum and frontal cortex. However, when the rats treated with a combination of N-tert-butyl-alpha-phenylnitrone and 3,4-methyl enedioxymethamphetamine were maintained at hyperthermic conditions, N- tert-butyl-alpha-phenylnitrone had no protective effect. These results suggest that body temperature plays a prominent role in the 3,4-methy lenedioxymethamphetamine-induce acute decrease in tryptophan hydroxyla se activity.