Initial deficit and recovery of function after MDMA preexposure in rats

Abstract

3,4-methylenedioxymethamphetamine (MDMA) exposure was reported to result in deficits in serotonergic neurotransmission with concomitant behavioral suppression and tolerance to MDMA. Some data have also suggested that the neurochemical deficits recover over time, raising the question as to whether behavioral suppression would show a similar recovery. The possibility of recovery of behavioral deficits was examined in the present study. Rats were administered an MDMA pretreatment regimen that was shown to produce numerous serotonergic deficits and behavioral suppression 2 weeks thereafter. The full expression of MDMA-produced hyperactivity was dependent upon serotonergic integrity, therefore, the present study aimed to determine whether MDMA pretreated rats were tolerant to MDMA 2 weeks after exposure. Further, because serotonergic deficits have shown recovery over time, similar behavioral tests were conducted at a later time point to determine whether functional recovery was evident. MDMA-produced hyperactivity was measured at different withdrawal periods (2 and 12 weeks) to determine initial effects and the possibility of recovery of function. In saline-pretreated control rats, +/-MDMA (0.0-10.0 mg/kg) produced a dose-dependent increase in locomotor activity. Rats that had received prior exposure to MDMA (4 x 10 mg/kg MDMA injections administered at 2 h intervals) demonstrated tolerance when the activity was measured 2 weeks after pretreatment. For these rats, there was a downward shift in the dose-effect curve for MDMA-produced hyperactivity. MDMA-produced hyperactivity in rats that were tested 12 weeks after pretreatment was, however, comparable to controls, suggesting recovery of function. These data are consistent with the idea that high dose MDMA exposure produces neuroadaptations that exhibit recovery with extended abstinence from the drug.