Antagonism of the neurotoxicity due to a single administration of methylenedioxymethamphetamine.
C J Schmidt, Christine K. Black, Vicki L. Taylor
European Journal of Pharmacology May 31, 1990 DOI: 10.1016/0014-2999(90)90245-2 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Animals (species not stated in the abstract) treated with MDMA |
| Interventions | MDMA Reserpine Monofluoromethyl DOPA Alpha-methyl-p-tyrosine 6-hydroxydopamine Haloperidol 5-HT2 antagonists |
| Topics | MDMA |
| Key findings | MDMA's long-term reductions in 5-HT concentration and tryptophan hydroxylase activity were prevented by depleting vesicular monoamines (reserpine), inhibiting monoamine synthesis (monofluoromethyl DOPA), blocking dopamine synthesis (alpha-methyl-p-tyrosine), lesioning the substantia nigra (6-hydroxydopamine), blocking dopamine receptors (haloperidol), or blocking 5-HT2 receptors. The authors argue the neurotoxicity depends on release of both dopamine and 5-HT. |
Abstract
The role of transmitter release in the serotonergic neurotoxicity of methylenedioxymethamphetamine (MDMA) was examined using treatments altering MDMA-induced release or its consequences. The long-term decrease in 5-HT concentrations and tryptophan hydroxylase activity produced by MDMA was antagonized by depletion of vesicular monoamines with reserpine or interruption of monoamine synthesis with the decarboxylase inhibitor, monofluoromethyl DOPA (dihydroxyphenylalanine). Similar results were achieved by selectively inhibiting dopamine synthesis with alpha-methyl-p-tyrosine or through bilateral lesions of the substantia nigra with 6-hydroxydopamine. The dopamine receptor antagonist haloperidol was also effective in this regard. Although these results strongly implicate dopamine release in the long-term neurochemical effects of MDMA, protection was also provided by selective 5-HT2 antagonists indicating that the neurotoxicity is dependent upon the release of both dopamine and 5-HT.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 34
- 3,4‐Methylenedioxymethamphetamine (MDMA, “Ecstasy”): pharmacology and toxicology in animals and humans Addiction May 1, 1994
- 5-HT2 receptors exert a state-dependent regulation of dopaminergic function: studies with MDL 100,907 and the amphetamine analogue, 3,4-methylenedioxymethamphetamine European Journal of Pharmacology November 1, 1992
- Potentiation of 3,4-methylenedioxymethamphetamine-induced dopamine release and serotonin neurotoxicity by 5-HT2 receptor agonists. European Journal of Pharmacology November 3, 1994
- Methylenedioxymethamphetamine-induced hyperthermia and neurotoxicity are independently mediated by 5-HT2 receptors Brain Research October 1, 1990
- Glutathione and N-Acetylcysteine Conjugates of α-Methyldopamine Produce Serotonergic Neurotoxicity: Possible Role in Methylenedioxyamphetamine-Mediated Neurotoxicity Chemical Research in Toxicology November 19, 1999
and 29 more in the library
Cites 8
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- Serotonergic-dopaminergic mediation of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy"). Pharmacology, Biochemistry, and Behavior December 1988
- Direct central effects of acute methylenedioxymethamphetamine on serotonergic neurons. European Journal of Pharmacology October 26, 1988
- Role of endogenous dopamine in the central serotonergic deficits induced by 3,4-methylenedioxymethamphetamine. Journal of Pharmacology and Experimental Therapeutics October 1, 1988
and 3 more in the library