Conclusions
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.
Methods
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.
Results
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. Conclusions: 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.