Reinstatement of extinguished amphetamine self-administration by 3,4-methylenedioxymethamphetamine (MDMA) and its enantiomers in rhesus monkeys
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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.