Studies on the role of dopamine in the degeneration of 5‐HT nerve endings in the brain of Dark Agouti rats following 3,4‐methylenedioxymethamphetamine (MDMA or ‘ecstasy’) administration
María Isabel Colado, Esther O’shea, R Granados, B. Moreno Esteban, Alicia Martín, A R Green
British Journal of Pharmacology February 1, 1999 DOI: 10.1038/sj.bjp.0702373 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Dark Agouti rats |
| Interventions | Haloperidol MDMA clomethiazole |
| Dose | 2 mg kg−1 i.p. haloperidol, 15 mg kg−1 i.p. MDMA, 25 mg kg−1 i.p. L-DOPA plus 6.25 mg kg−1 i.p. benserazide, 50 mg kg−1 i.p. clomethiazole |
| Duration | 7 days post-MDMA for neurodegeneration assessment |
| Topics | MDMA |
| Keywords | Microdialysis Dopamine Pharmacology Haloperidol Neurodegeneration Neurotoxicity Methamphetamine Benserazide Endocrinology |
| Citations | 82 |
| Key findings | Dopamine does not mediate MDMA-induced neurodegeneration of serotonin nerve endings; the protective effect of haloperidol is primarily due to preventing hyperthermia. |
Abstract
We investigated whether dopamine plays a role in the neurodegeneration of 5‐hydroxytryptamine (5‐HT) nerve endings occurring in Dark Agouti rat brain after 3,4‐methylenedioxymethamphetamine (MDMA or ‘ecstasy’) administration. Haloperidol (2 mg kg −1 i.p.) injected 5 min prior and 55 min post MDMA (15 mg kg −1 i.p.) abolished the acute MDMA‐induced hyperthermia and attenuated the neurotoxic loss of 5‐HT 7 days later. When the rectal temperature of MDMA+haloperidol treated rats was kept elevated, this protective effect was marginal. MDMA (15 mg kg −1 ) increased the dopamine concentration in the dialysate from a striatal microdialysis probe by 800%. L ‐DOPA (25 mg kg −1 i.p., plus benserazide, 6.25 mg kg −1 i.p.) injected 2 h after MDMA (15 mg kg −1 ) enhanced the increase in dopamine in the dialysate, but subsequent neurodegeneration was unaltered. L ‐DOPA (25 mg kg −1 ) injected before a sub‐toxic dose of MDMA (5 mg kg −1 ) failed to induce neurodegeneration. The MDMA‐induced increase in free radical formation in the hippocampus (indicated by increased 2,3‐ and 2,5‐dihydroxybenzoic acid in a microdialysis probe perfused with salicylic acid) was unaltered by L ‐DOPA. The neuroprotective drug clomethiazole (50 mg kg −1 i.p.) did not influence the MDMA‐induced increase in extracellular dopamine. These data suggest that previous observations on the protective effect of haloperidol and potentiating effect of L ‐DOPA on MDMA‐induced neurodegeneration may have resulted from effects on MDMA‐induced hyperthermia. The increased extracellular dopamine concentration following MDMA may result from effects of MDMA on dopamine re‐uptake, monoamine oxidase and 5‐HT release rather than an ‘amphetamine‐like’ action on dopamine release, thus explaining why the drug does not induce degeneration of dopamine nerve endings. British Journal of Pharmacology (1999) 126 , 911–924; doi: 10.1038/sj.bjp.0702373
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 28
- The pharmacology of the acute hyperthermic response that follows administration of 3,4‐methylenedioxymethamphetamine (MDMA, ‘ecstasy’) to rats British Journal of Pharmacology 2002
- A study of the mechanisms involved in the neurotoxic action of 3,4‐methylenedioxymethamphetamine (MDMA, ‘ecstasy’) on dopamine neurones in mouse brain British Journal of Pharmacology December 1, 2001
- 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
- Neurotoxicity of MDMA: Main effects and mechanisms. Experimental Neurology October 1, 2021
and 23 more in the library
Cites 33
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- Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Journal of Pharmacology and Experimental Therapeutics 1987
- 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
- 3,4‐Methylenedioxymethamphetamine (MDMA, “Ecstasy”): pharmacology and toxicology in animals and humans Addiction May 1, 1994
- Neurotoxicity of MDMA and Related Compounds: Anatomic Studiesa Annals of the New York Academy of Sciences October 1, 1990
and 28 more in the library