BIOCHEMICAL AND HISTOLOGICAL EVIDENCE THAT METHYLENEDIOXYMETHYLAMPHETAMINE (MDMA) IS TOXIC TO NEURONS IN THE RAT-BRAIN
- 1 April 1987
- journal article
- research article
- Vol. 241 (1) , 338-346
Abstract
(.+-.)-3,4-Methylenedioxymethylamphetamine (MDMA) was administered s.c. to rats (10, 20 or 40 mg/kg b. wt.) and guinea pigs (20 mg/kg) twice a day for 4 days, 2 weeks before decapitation. Norepinephrine, dopamine and serotonin (5-HT) levels were assayed in the hippocampus, hypothalamus, striatum and neocortex. In rats, MDMA produced dose-dependent reductions in 5-HT in all brain regions examined. the highest dose also reduced norepinephrine and/or dopmaine in some regions. The 20-mg/kg dose of MDMA depeted 5-HT in all regions of the guinea pig brain assayed. In both species, repeated administration of 20 mg/kg of MDMA reduced the Vmax but not the Km of 5-HT uptake 2 weeks after adminstration. A single 40-mg/kg injection of MDMA depleted 5-HT 2 and 8 weeks after administration to rats in all regions of the brain examined except the hypothalamus. Administration of 80 mg/kg of MDMA twice a day for 2 days to rats depleted striatal 5-HT and dopamine. Brain sections from rats injected from MDMA according to this dosage regimen were stained by the Fink-Heimer method. Degenerating axon terminals and cell bodies were observed in the striatum and somatosensory cortex, respectively. These findings suggest that MDMA is toxic to serotonergic and, to a lesser extent, catecholaminergic neurons. Some neurons that do not contain these transmitters (neocortical neurons) are also affected.This publication has 15 references indexed in Scilit:
- Long-term effects of repeated methylamphetamine administration on dopamine and serotonin neurons in the rat brain: A regional studyBrain Research, 1980
- Amphetamine induces depletion of dopamine and loss of dopamine uptake sites in caudateNeurology, 1980
- Chronic amphetamine administration decreases brain tryptophan hydroxylase activity in catsLife Sciences, 1980
- LONG-TERM EFFECTS OF MULTIPLE DOSES OF METHAMPHETAMINE ON TRYPTOPHAN-HYDROXYLASE AND TYROSINE-HYDROXYLASE ACTIVITY IN RAT-BRAIN1980
- Methamphetamine-induced changes in brain catecholamines in rats and guinea pigsDrug and Alcohol Dependence, 1979
- EFFECT OF DEPLETION OF BRAIN DOPAMINE BY 6-HYDROXYDOPAMINE ON TOLERANCE TO THE ANOREXIC EFFECT OF D-AMPHETAMINE AND FENFLURAMINE IN RATS1979
- Long-Term Changes in Dopaminergic Innervation of Caudate Nucleus After Continuous Amphetamine AdministrationScience, 1978
- Evaluation of the neurotoxic effects of p-chloroamphetamine: A histological and biochemical studyNeuropharmacology, 1978
- COMPARISON BETWEEN NEUROTOXIC AND SEROTONIN-DEPLETING EFFECTS OF VARIOUS HALOGENATED DERIVATIVES OF AMPHETAMINE IN RAT1977
- OXYGEN-DEPENDENT REACTION OF 6-HYDROXYDOPAMINE, 5,6-DIHYDROXYTRYPTAMINE, AND RELATED COMPOUNDS WITH PROTEINS INVITRO - MODEL FOR CYTOTOXICITY1976