Rats preexposed to MDMA display attenuated responses to its aversive effects in the absence of persistent monoamine depletions

Abstract

Rationale: The abuse potential of a given drug may be mediated by both its rewarding and aversive effects, the latter of which are often far less characterized.

Objectives: Using the conditioned taste-aversion (CTA) preparation, the present experiments examined changes in the aversive effects of the commonly used recreational drug MDMA following repeated drug exposures.

Methods: Experiment 1 used three varying doses of MDMA (1.0, 1.8, and 3.2 mg/kg) to determine a dose that produced taste aversions of intermediate strength. Experiments 2 and 3 characterized the effects of repeated preexposures to MDMA (1.8 or 3.2 mg/kg) on taste aversions induced by MDMA (1.8 mg/kg). Additionally, levels of several monoamines and metabolites were analyzed in frontal cortex and caudate-putamen from subjects in Experiment 3 to assess for persistent monoamine depletions.

Results: MDMA induced dose-dependent taste aversions. Preexposure to MDMA (at both doses) resulted in an attenuation of MDMA-induced taste aversions. These effects were not likely due to persistent monoamine depletions, as subjects preexposed to the higher MDMA dose did not differ from controls in levels of monoamines or metabolites in either brain region examined.

Conclusions: Prior MDMA experience weakened the ability of MDMA to induce taste aversions. This attenuation of MDMA's aversive effects may occur with low doses that do not persistently alter monoamine levels.