Dissociation of the neurochemical and behavioral toxicology of MDMA ('Ecstasy') by citalopram.
Brian J. Piper, Joseph B. Fraiman, Cullen B Owens, Syed F. Ali, Jerrold S. Meyer
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology April 2008 DOI: 10.1038/sj.npp.1301491 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 67 |
| Population | Male Sprague-Dawley rats |
| Interventions | MDMA Citalopram |
| Dose | MDMA 4 x 10 mg/kg; citalopram 10 mg/kg |
| Duration | 10 weeks |
| Topics | MDMA |
| Key findings | Citalopram pretreatment blocked MDMA-induced reductions in aggressive and exploratory behavior and protected against serotonin neurotoxicity at one week, but did not prevent acute hyperthermia, weight loss, or decreased motor activity one day after dosing, suggesting some consequences are mediated by non-serotonergic mechanisms. |
Abstract
High or repeated doses of the recreational drug 3,4-methylenedioxymethamphetamine (MDMA, or 'Ecstasy') produce long-lasting deficits in several markers of serotonin (5-HT) system integrity and also alter behavioral function. However, it is not yet clear whether MDMA-induced serotonergic neurotoxicity is responsible for these behavioral changes or whether other mechanisms are involved. The present experiment tested the hypothesis that blocking serotonergic neurotoxicity by pretreatment with the selective 5-HT reuptake inhibitor citalopram will also prevent the behavioral and physiological consequences of an MDMA binge administration. Male, Sprague-Dawley rats (N=67) received MDMA (4 x 10 mg/kg) with or without citalopram (10 mg/kg) pretreatment. Core temperature, ejaculatory response, and body weight were monitored during and immediately following drug treatments. A battery of tests assessing motor, cognitive, exploratory, anxiety, and social behaviors was completed during a 10-week period following MDMA administration. Brain tissue was collected at 1 and 10 weeks after drug treatments for measurement of regional 5-HT transporter binding and (for the 1-week samples) 5-HT and 5-HIAA concentrations. Citalopram pretreatment blocked MDMA-related reductions in aggressive and exploratory behavior measured in the social interaction and hole-board tests respectively. Such pretreatment also had the expected protective effect against MDMA-induced 5-HT neurotoxicity at 1 week following the binge. In contrast, citalopram did not prevent most of the acute effects of MDMA (eg hyperthermia and weight loss), nor did it block the decreased motor activity seen in the binge-treated animals 1 day after dosing. These results suggest that some of the behavioral and physiological consequences of a high-dose MDMA regimen in rats are mediated by mechanisms other than the drug's effects on the serotonergic system. Elucidation of these mechanisms requires further study of the influence of MDMA on other neurotransmitter systems.