Understanding the neuroadaptations underlying the effects of (+)-methylenedioxymethamphetamine [(+)-MDMA; ecstasy]: Implications for the serotonin 5-HT2A receptor and its binding partners

Repeated administration of 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”) induces “behavioral sensitization,” an enhancement of its behavioral effects. The molecular changes underlying behavioral sensitization may be linked to neuropsychological sequelae (e.g., depression, anxiety) seen upon withdrawal from MDMA exposure. Microarray analyses were conducted following administration of a behaviorally sensitizing, non-neurotoxic regimen of (+)-MDMA (4 mg/kg/day, 7 days) to identify patterns of neuroadaptations within the brain “reward” circuit. Differential expression of the mRNA for the serotonin 5-HT2A receptor, a known modulator of the behavioral effects of MDMA, and its binding partners, were observed at 24 hrs withdrawal. However, these results were not validated by quantitative RT-PCR nor did Western blot analyses reveal a disruption in the expression of these proteins. Thus, altered expression of the proteins studied herein does not appear to underlie the expression of behavioral sensitization to (+)-MDMA. Future experiments are required to analyze the function of binding partners in the regulation of 5-HT2AR.