Body temperature effect on methylenedioxymethamphetamine-induced acute decrease in tryptophan hydroxylase activity.
S Che, M Johnson, Glen R. Hanson, James W. Gibb
European Journal of Pharmacology December 1, 1995 DOI: 10.1016/0926-6917(95)90065-9 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Rats (Sprague-Dawley implied by context; not stated in abstract) |
| Interventions | 3 4-methylenedioxymethamphetamine N-tert-butyl-alpha-phenylnitrone |
| Dose | 3,4-methylenedioxymethamphetamine 20 mg/kg, s.c.; N-tert-butyl-alpha-phenylnitrone 200 mg/kg, i.p. |
| Duration | 2 h after drug treatment |
| Topics | MDMA |
| Keywords | Brain stem Hippocampus Corpus striatum Cerebral cortex Animals Rats, sprague-dawley Nitrogen oxides N-methyl-3,4-methylenedioxyamphetamine Cyclic n-oxides Tryptophan hydroxylase Serotonin agents Free radical scavengers Body temperature Drug interactions Male |
| Key findings | MDMA (20 mg/kg) decreased tryptophan hydroxylase activity in rat hippocampus, striatum, and frontal cortex to 61%, 65%, and 71% of control levels, respectively, when rats were hyperthermic, but had no effect when rats were hypothermic. The authors conclude that body temperature plays a prominent role in the acute MDMA-induced decrease in tryptophan hydroxylase activity, possibly via free radical formation. |
Abstract
Brain tryptophan hydroxylase activity decreases within 15 min after a single administration of 3,4-methylenedioxymethamphetamine. In the present study, the effect of body temperature on this acute decrease of tryptophan hydroxylase activity was examined. 2 h after a single dose of 3,4-methylenedioxymethamphetamine (20 mg/kg, s.c.), rats exhibited hyperthermia (38.7 degrees C) or hypothermia (35.8 degrees C) when maintained at 25 degrees C or 6 degrees C, respectively. The rectal temperature of control animals maintained at 6 degrees C was not altered. Tryptophan hydroxylase activity measured in the hippocampus, striatum and frontal cortex of hyperthermic rats treated with 3,4-methylenedioxymethamphetamine was decreased to 61%, 65%, and 71% of control levels, respectively, 2 h after drug treatment. However, in hypothermic rats, 3,4-methylenedioxymethamphetamine had no effect on tryptophan hydroxylase activity in the hippocampus, striatum or frontal cortex. Non-drug-induced hyperthermia or hypothermia did not affect tryptophan hydroxylase activity. Since hypothermia may prevent the 3,4-methylenedioxymethamphetamine-induced decrease in tryptophan hydroxylase activity by reducing the formation of free radicals, the effect of a free radical scavenging agent, N-tert-butyl-alpha-phenylnitrone, was examined. N-tert-butyl-alpha-phenylnitrone (200 mg/kg, i.p.) alone caused hypothermia but had no direct effect on tryptophan hydroxylase activity. Preadministration of N-tert-butyl-alpha-phenylnitrone prevented 3,4-methylenedioxymethamphetamine from raising the temperature above normal and attenuated the drug-induced decrease in tryptophan hydroxylase activity in hippocampus, striatum and frontal cortex. However, when the rats treated with a combination of N-tert-butyl-alpha-phenylnitrone and 3,4-methylenedioxymethamphetamine 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-methylenedioxymethamphetamine-induced acute decrease in tryptophan hydroxylase activity.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 8
- Small Changes in Ambient Temperature Cause Large Changes in 3,4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonin Neurotoxicity and Core Body Temperature in the Rat Journal of Neuroscience July 1, 1998
- Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms Pharmacological Reviews December 16, 2020
- Aged rats are more vulnerable than adolescents to "ecstasy"-induced toxicity. Archives of Toxicology July 2018
- Low ambient temperature reveals distinct mechanisms for MDMA-induced serotonergic toxicity and astroglial Hsp27 heat shock response in rat brain. Neurochemistry International July 5, 2011
- Acute concomitant effects of MDMA binge dosing on extracellular 5-HT, locomotion and body temperature and the long-term effect on novel object discrimination in rats. Psychopharmacology July 20, 2010
and 3 more in the library
Cites 9
- Methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: immunocytochemical evidence for neurotoxicity Journal of Neuroscience August 1, 1988
- 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Journal of Pharmacology and Experimental Therapeutics September 1, 1987
- Methylenedioxymethamphetamine-induced hyperthermia and neurotoxicity are independently mediated by 5-HT2 receptors Brain Research October 1, 1990
- Toxicity and deaths from 3,4-methylenedioxymethamphetamine ("ecstasy"). The Lancet August 15, 1992
- Metabolism of methylenedioxymethamphetamine: formation of dihydroxymethamphetamine and a quinone identified as its glutathione adduct. Journal of Pharmacology and Experimental Therapeutics August 1, 1990
and 4 more in the library