Methylphenidate and MDMA adolescent exposure in mice: long-lasting consequences on cocaine-induced reward and psychomotor stimulation in adulthood.

Pre-exposure to psychostimulants enhances the rewarding and psychomotor stimulating effects of subsequent drug exposure. Currently, there is a prevalence of adolescent exposure to the psychostimulants methylphenidate (MPD) and 3,4-methylenedioxymethamphetamine (MDMA). However, there is a paucity of investigation concerning the long-term behavioral consequences of exposure to these stimulants during adolescence. The aim of the present study was to investigate the effect of MPD and MDMA exposure in adolescence on cocaine-induced reward and psychomotor stimulation in adulthood. Adolescent Swiss-Webster mice received intraperitoneal injections of saline, MPD (10 mg/kg) or MDMA (10 mg/kg) from PD 26 to PD 32. Animal weights were monitored during and after drug administration. One month later, cocaine-induced conditioned place preference (CPP) and locomotor activity (LMA) were investigated. MPD and MDMA inhibited weight increase from PD 28 to PD 39 compared to the saline group, but weights amongst the three groups equalized by PD 46. MDMA exposure resulted in the same magnitude of cocaine (20 mg/kg)-induced CPP as saline exposure; however, MPD exposure caused significantly less CPP. Two weeks following extinction of CPP and withdrawal from cocaine, a priming injection of cocaine (5 mg/kg) reinstated significantly higher CPP in the MPD and MDMA groups than in the saline group. In the LMA experiments, cocaine (15 mg/kg) was administered for 5 consecutive days. On days 1 and 5, cocaine-induced hyperlocomotion in the MPD group was significantly higher than in the saline and MDMA groups. After a 2-week withdrawal period, cocaine (5 mg/kg) evoked significantly higher LMA responses in the MPD and MDMA groups compared to the saline group. Results suggest that exposure of mice to both MPD and MDMA during adolescence involves long-lasting neural adaptations, manifested as sensitized responses to cocaine-induced reward and psychomotor stimulation following cocaine withdrawal.