Achat-Mendes C, Anderson KL, Itzhak Y. (2003) Methylphenidate and MDMA adolescent exposure in mice: long-lasting consequences on cocaine-induced reward and psychomotor stimulation in adulthood. Neuropharmacology 45:106-115.

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Researchers compared MDMA with methylphenidate (Ritalin) on capacity to alter (enhance or diminish) the rewarding effects of cocaine in group-housed Swiss-Webster mice. Mice received either daily i.p. injections of 10 mg/kg methylphenidate or 10 mg/kg MDMA from postnatal day (PD) 26 to PD 32 (6 days), considered mouse "adolescence." 30 days post-drug (PND62), mice underwent conditioned place preference (CPP) training with 20 mg/kg cocaine, and CPP was assessed after 10 days of training. CPP (time spent in drug-associated compartment) was assessed on PD73. Extinction of CPP (through no longer providing cocaine) was performed over 14 days, and assessed on the 15th day (PD88), then cocaine was reinstated a day later. Cocaine-associated increases in locomotor activity was assessed 30 days post-drug (PD62) by administering either saline or 15 mg/kg cocaine and measuring activity via photobeam interruption. Locomotor activity was assessed for 5 days (PD62-PD67), and again after a 14-day drug-free period (on PD81) with 5 mg/kg cocaine. MDMA-treated and saline-treated animals developed equally strong CPP for cocaine, while methylphenidate-treated mice developed lower CPP. CPP extinction was successful in all 3 groups. When cocaine was reinstated, both methylphenidate-treated and MDMA-treated mice showed greater CPP than saline-treated mice. Methylphenidate pretreatment increased cocaine-induced locomotor activity above levels seen in saline-treated mice on Day 1 of assessment, whereas MDMA pre-treatment did not have this effect. Methylphenidate-pretreated mice were more active than saline-pretreated mice on Day 5 of cocaine treatment, and there was a trend for MDMA-pretreated mice to be more active than saline-treated animals on Day 5. Both MDMA-pretreated and methylphenidate pretreated mice were more active after 5 mg/kg cocaine than saline-pretreated mice. The researchers interpret findings from the first study as indicating that exposure to methylphenidate or MDMA during adolescence may increase susceptibility to cocaine’s rewarding effects, despite an apparent reduction in cocaine-associated CPP soon after methylphenidate pretreatment. No histological examinations were performed, so it is unknown whether behavioral changes assessed were associated with neurotoxicity. In contrast to findings reported in this study, a previous study with the same mouse strain found repeated doses of MDMA enhanced locomotor activity after cocaine (Itzhak et al. 2003), but higher and more frequent doses were used in that study. MDMA pretreatment may also enhance the rewarding effects of cocaine in rats (Fletcher et al. 2001; Fone et al. 2002). It is unclear how well rodent "adolescence" is analogous to human puberty, but this study, like those before it, suggests that early exposure to methylphenidate and MDMA could increase rewarding properties of other drugs slightly later on in life.