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Dissociation of the neurochemical and behavioral toxicology of MDMA ('Ecstasy') by citalopram.
Neuropsychopharmacology 2008; 33(5):1192-205N

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.

Authors+Show Affiliations

Neuroscience and Behavior Program, University of Massachusetts, Amherst, MA, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17609680

Citation

Piper, Brian J., et al. "Dissociation of the Neurochemical and Behavioral Toxicology of MDMA ('Ecstasy') By Citalopram." Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, vol. 33, no. 5, 2008, pp. 1192-205.
Piper BJ, Fraiman JB, Owens CB, et al. Dissociation of the neurochemical and behavioral toxicology of MDMA ('Ecstasy') by citalopram. Neuropsychopharmacology. 2008;33(5):1192-205.
Piper, B. J., Fraiman, J. B., Owens, C. B., Ali, S. F., & Meyer, J. S. (2008). Dissociation of the neurochemical and behavioral toxicology of MDMA ('Ecstasy') by citalopram. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, 33(5), pp. 1192-205.
Piper BJ, et al. Dissociation of the Neurochemical and Behavioral Toxicology of MDMA ('Ecstasy') By Citalopram. Neuropsychopharmacology. 2008;33(5):1192-205. PubMed PMID: 17609680.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dissociation of the neurochemical and behavioral toxicology of MDMA ('Ecstasy') by citalopram. AU - Piper,Brian J, AU - Fraiman,Joseph B, AU - Owens,Cullen B, AU - Ali,Syed F, AU - Meyer,Jerrold S, Y1 - 2007/07/04/ PY - 2007/7/5/pubmed PY - 2008/8/2/medline PY - 2007/7/5/entrez SP - 1192 EP - 205 JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JO - Neuropsychopharmacology VL - 33 IS - 5 N2 - 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. SN - 0893-133X UR - https://www.unboundmedicine.com/medline/citation/17609680/Dissociation_of_the_neurochemical_and_behavioral_toxicology_of_MDMA__'Ecstasy'__by_citalopram_ L2 - http://dx.doi.org/10.1038/sj.npp.1301491 DB - PRIME DP - Unbound Medicine ER -