Reinstatement of extinguished amphetamine self-administration by 3,4-methylenedioxymethamphetamine (MDMA) and its enantiomers in rhesus monkeys.
Jessica McClung, William E Fantegrossi, Leonard L. Howell
Psychopharmacology May 2010 DOI: 10.1007/s00213-010-1818-7 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Peer reviewed |
|---|---|
| Sample size | 4 |
| Population | Rhesus monkeys self-administering intravenous amphetamine |
| Interventions | Amphetamine BZP SR(+/-)-MDMA S(+)-MDMA R(-)-MDMA fenfluramine fluoxetine |
| Topics | MDMA |
| Key points | Amphetamine, BZP, racemic MDMA, and S(+)-MDMA priming injections significantly reinstated responding previously maintained by amphetamine self-administration, whereas R(-)-MDMA and fenfluramine did not. Fluoxetine pretreatment attenuated reinstatement by racemic MDMA, S(+)-MDMA, and BZP but not amphetamine. The authors suggest MDMA's reinstatement effects are mediated primarily by dopamine release, with serotonergic mechanisms contributing at least partially. |
Abstract
The effectiveness of MDMA and its enantiomers to reinstate responding previously maintained by drug self-administration has not been thoroughly investigated. The present study was designed to compare the reinstatement effects of amphetamine, the piperazine-analog BZP, SR(+/-)-MDMA, S(+)-MDMA, R(-)-MDMA, and fenfluramine on behavior maintained under a second-order schedule of intravenous amphetamine self-administration in rhesus monkeys (n=4). Following saline substitution and extinction, a range of doses of amphetamine, BZP, SR(+/-)-MDMA, S(+)-MDMA, R(-)-MDMA, and fenfluramine were administered i.v. as non-contingent priming injections in order to characterize their effectiveness to reinstate responding previously maintained by amphetamine self-administration. Priming injections of amphetamine, BZP, SR(+/-)-MDMA, and S(+)-MDMA induced significant reinstatement effects. In contrast, neither R(-)-MDMA nor fenfluramine effectively reinstated behavior. Pretreatment with the selective serotonin transporter inhibitor, fluoxetine, attenuated the reinstatement effects of SR(+/-)-MDMA, S(+)-MDMA, and BZP but had no significant effect on amphetamine-primed reinstatement. Given the profile of neurochemical effects published previously, these findings suggest that the reinstatement effects of MDMA are mediated primarily by dopamine release; however, the attenuation of MDMA-induced reinstatement by fluoxetine supports previous research demonstrating the complex behavioral pharmacology of MDMA-like drugs and that the reinstatement effects of MDMA are at least partially mediated by serotonergic mechanisms.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 8
- 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
- Acute effects of R-MDMA, S-MDMA, and racemic MDMA in a randomized double-blind cross-over trial in healthy participants. Neuropsychopharmacology December 1, 2024
- Acute effects of 3,4-methylenedioxymethamphetamine (MDMA) and R(-) MDMA on actigraphy-based daytime activity and sleep parameters in rhesus monkeys. Experimental and Clinical Psychopharmacology June 25, 2018
- (±)-MDMA and its enantiomers: potential therapeutic advantages of R(-)-MDMA. Psychopharmacology February 2018
- Serotonin antagonists fail to alter MDMA self-administration in rats. Pharmacology, Biochemistry, and Behavior September 2016
and 3 more in the library
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