A comparative study on the acute and long‐term effects of MDMA and 3,4‐dihydroxymethamphetamine (HHMA) on brain monoamine levels after i.p. or striatal administration in mice
Isabel Escobedo, Esther O’shea, Laura Orío, Verónica Sánchez, Mireia Segura, Rafael de la Torre, Magı́ Farré, Alfred Richard Green, María Isabel Colado
British Journal of Pharmacology 2005 DOI: 10.1038/sj.bjp.0706071 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mouse |
| Interventions | MDMA HHMA |
| Dose | 30 mg kg −1 three times at 3‐h intervals (MDMA i.p.); 1, 10 and 100 μg three times at 3‐h intervals (intrastriatal MDMA) |
| Duration | Acute effects measured 1 hour after last dose; long-term effects measured 7 days later |
| Topics | MDMA Serotonin |
| Keywords | Dopamine Monoamine neurotransmitter Neurotoxicity Pharmacology Striatum Metabolite Endocrinology |
| Citations | 68 |
| Key findings | MDMA's parent compound is not responsible for acute monoamine release or long-term dopamine depletion in mouse striatum, and the metabolite HHMA does not account for these effects. |
Abstract
This study investigated whether the immediate and long‐term effects of 3,4‐methylenedioxymethamphetamine (MDMA) on monoamines in mouse brain are due to the parent compound and the possible contribution of a major reactive metabolite, 3,4‐dihydroxymethamphetamine (HHMA), to these changes. The acute effect of each compound on rectal temperature was also determined. MDMA given i.p. (30 mg kg −1 , three times at 3‐h intervals), but not into the striatum (1, 10 and 100 μ g, three times at 3‐h intervals), produced a reduction in striatal dopamine content and modest 5‐HT reduction 1 h after the last dose. MDMA does not therefore appear to be responsible for the acute monoamine release that follows its peripheral injection. HHMA does not contribute to the acute MDMA‐induced dopamine depletion as the acute central effects of MDMA and HHMA differed following i.p. injection. Both compounds induced hyperthermia, confirming that the acute dopamine depletion is not responsible for the temperature changes. Peripheral administration of MDMA produced dopamine depletion 7 days later. Intrastriatal MDMA administration only produced a long‐term loss of dopamine at much higher concentrations than those reached after the i.p. dose and therefore bears little relevance to the neurotoxicity. This indicates that the long‐term effect is not attributable to the parent compound. HHMA also appeared not to be responsible as i.p. administration failed to alter the striatal dopamine concentration 7 days later. HHMA was detected in plasma, but not in brain, following MDMA (i.p.), but it can cross the blood–brain barrier as it was detected in the brain following its peripheral injection. The fact that the acute changes induced by i.p. or intrastriatal HHMA administration differed indicates that HHMA is metabolised to other compounds which are responsible for changes observed after i.p. administration. British Journal of Pharmacology (2005) 144 , 231–241. doi: 10.1038/sj.bjp.0706071
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 33
- 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings Psychopharmacology March 15, 2006
- A review of acute effects of 3,4-methylenedioxymethamphetamine in healthy volunteers Journal of Psychopharmacology March 1, 2006
- Dopamine D2-receptor knockout mice are protected against dopaminergic neurotoxicity induced by methamphetamine or MDMA Neurobiology of Disease March 22, 2021
- The ugly side of amphetamines: short- and long-term toxicity of 3,4-methylenedioxymethamphetamine (MDMA, ‘Ecstasy’), methamphetamine and d-amphetamine Biological Chemistry January 2, 2011
- Metabolites of the ring-substituted stimulants MDMA, methylone and MDPV differentially affect human monoaminergic systems Journal of Psychopharmacology April 30, 2019
and 28 more in the library
Cites 9
- Positron emission tomographic evidence of toxic effect of MDMA (“Ecstasy”) on brain serotonin neurons in human beings The Lancet October 1, 1998
- The pharmacology of the acute hyperthermic response that follows administration of 3,4‐methylenedioxymethamphetamine (MDMA, ‘ecstasy’) to rats British Journal of Pharmacology 2002
- In vivo evidence for free radical involvement in the degeneration of rat brain 5‐HT following administration of MDMA (‘ecstasy’) and p‐chloroamphetamine but not the degeneration following fenfluramine British Journal of Pharmacology July 1, 1997
- 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
and 4 more in the library