Effect of acute monoamine depletion on 3,4-methylenedioxymethamphetamine-induced neurotoxicity.
J Brodkin, A Malyala, J F Nash
Pharmacology, Biochemistry, and Behavior July 1, 1993 DOI: 10.1016/0091-3057(93)90520-4 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Rats (striatum and frontal cortex tissue; in vivo microdialysis) |
| Interventions | 3 4-methylenedioxymethamphetamine (MDMA) alpha-methyl-p-tyrosine (alpha-MPT) p-chlorophenylalanine (PCPA) |
| Duration | 7-day follow-up |
| Measures | in vivo microdialysis, 5-HT content, DA efflux, 5-HT uptake sites |
| Topics | Serotonin MDMA |
| Keywords | Axons Nerve endings Animals Rats, sprague-dawley Nervous system diseases Biogenic monoamines Dopamine N-methyl-3,4-methylenedioxyamphetamine Paroxetine Tyrosine 3-monooxygenase Fenclonine Methyltyrosines Alpha-methyltyrosine Receptors, serotonin Designer drugs Stereotaxic techniques Dialysis Brain chemistry Male |
| Key findings | The authors report that depleting dopamine with alpha-methyl-p-tyrosine blocked the long-term (7-day) depletion of striatal serotonin content after MDMA, whereas depleting serotonin with p-chlorophenylalanine did not prevent MDMA-induced loss of serotonin uptake sites in the frontal cortex. They argue that dopamine, not serotonin, plays a major role in MDMA's long-term neurotoxic effects on serotonin axon terminals. |
Abstract
The effect of acute, reversible depletion of either serotonin [5-hydroxytryptamine (5-HT)] or dopamine (DA) on the long-term (7-day) decrease of brain 5-HT content produced after 3,4-methylenedioxymethamphetamine (MDMA) administration was investigated. The tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine (alpha-MPT) significantly attenuated the acute increase in DA efflux produced by MDMA in the striatum as measured by in vivo microdialysis. Treatment with alpha-MPT had no effect on MDMA-induced 5-HT release. alpha-MPT treatment blocked the long-term (7-day) depletion of striatal 5-HT content after MDMA administration. The tryptophan hydroxylase inhibitor p-chlorophenylalanine (PCPA) completely blocked the acute increase in the extracellular concentration of 5-HT produced by MDMA. Although PCPA significantly attenuated the increase in DA efflux produced by MDMA, the effect was small in magnitude. More importantly, treatment with PCPA had no effect on MDMA-induced decrease of 5-HT uptake sites in the frontal cortex. These data are suggestive that acute depletion of DA but not 5-HT protects against the long-term neurotoxic effects of MDMA on 5-HT axon terminals. In addition, these data are supportive of the hypothesis that DA plays a major role in the neurotoxic effects of MDMA.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 21
- Potentiation of 3,4-methylenedioxymethamphetamine-induced dopamine release and serotonin neurotoxicity by 5-HT2 receptor agonists. European Journal of Pharmacology November 3, 1994
- Blockade of Striatal 5‐Hydroxytryptmine2Receptors Reduces the Increase in Extracellullar Concentrations of Dopamine Produced by the Amphhetamine analogue 3,4‐Methylenedioxymethamphetamine Journal of Neurochemistry April 1, 1994
- The mechanisms involved in the long‐lasting neuroprotective effect of fluoxetine against MDMA (‘ecstasy’)‐induced degeneration of 5‐HT nerve endings in rat brain British Journal of Pharmacology September 1, 2001
- Ascorbic acid prevents 3,4-methylenedioxymethamphetamine (MDMA)-induced hydroxyl radical formation and the behavioral and neurochemical consequences of the depletion of brain 5-HT Synapse 2001
- The abused drug MDMA (Ecstasy) induces programmed death of human serotonergic cells The FASEB Journal February 1, 1997
and 16 more in the library
Cites 16
- Methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: immunocytochemical evidence for neurotoxicity Journal of Neuroscience August 1, 1988
- Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Journal of Pharmacology and Experimental Therapeutics 1987
- Neuroanatomic specificity and time course of alterations in rat brain serotonergic pathways induced by MDMA (3,4‐methylenedioxymethamphetamine): Assessment using quantitative autoradiography Synapse August 1, 1991
- Methamphetamine neurotoxicity and striatal glutamate release: comparison to 3,4-methylenedioxymethamphetamine. Brain Research May 1, 1992
- Effects of 3,4-dihydroxymethamphetamine and 2,4,5-trihydroxymethamphetamine, two metabolites of 3,4-methylenedioxymethamphetamine, on central serotonergic and dopaminergic systems. Journal of Pharmacology and Experimental Therapeutics May 1, 1992
and 11 more in the library