| Description |
Brain tryptophan hydroxylase (TPH) activity decreases within 15 minutes after a single administration of 3,4-methylenedioxymethamphetamine (MDMA). The purpose of this study was to examine the effect of body temperature on the acute decrease of TPH activity and to elucidate the mechanism of the effect. Two hours after a single dose of MDMA (20 mg/kg, s.c), rats exhibited hyperthermia (38.7 °C) or hypothermia (35.8° C) when maintained at 25° C or 6° C, respectively. The rectal temperature of control animals maintained at 6° C was not altered. TPH activity measured in the hippocampus, striatum and frontal cortex of hyperthermic rats treated with MDMA was decreased to 61%, 65%, and 71% of control levels, respectively, 2 hours after drug treatment. However, in hypothermic rats, MDMA had no effect on TPH activity in the hippocampus, striatum or frontal cortex. This protection was not due to the increase of TPH activity caused by cold stress-induced phosphorylation. Non-drug-induced hyperthermia or hypothermia did not affect TPH activity. When tissue homogenates containing TPH were incubated in vitro with MDMA at 39.0° C, the drug had no effect on the enzyme activity. Since hypothermia may prevent the MDMA-induced decrease in TPH activity by reducing the formation of free radicals, the effect of a free radical scavenging agent, N-tert-butyl-alpha-phenylnitrone (BPN), was examined. BPN (200 mg/kg, i.p.) alone caused hypothermia but had no direct effect on TPH activity. Preadministration of BPN blocked the MDMA-induced hyperthermia and attenuated the drug-induced decrease in TPH activity in hippocampus, striatum and frontal cortex. The effect of MDMA on in vitro dopamine (DA) release at 35.5° C, 37.4° C or 39.0° C was examined. Incubation temperature had no effect on MDMA-induced DA release. These results suggest that body temperature affects the MDMA-induced rapid decrease in TPH activity in intact animals and this effect is not due to phosphorylation or altered in vitro DA release. Free radicals might be involved in the rapid neurochemical changes induced by MDMA. |
