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This study analyzed the role of dopamine D1 and D2 receptors in methylphenidate (MPH) conditioned place preference (CPP) in adolescent male and female rats, in addition to the role of these receptors in the effects of MPH on brain-derived neurotrophic factor (BDNF) in the dorsal striatum and nucleus accumbens. Using a nonbiased CPP procedure, the animals were conditioned from postnatal day (PD) 33 to 37. On conditioning trials, animals were first administered saline or their respective antagonist (0.1 or 0.2 mg/kg SCH-23390; 0.01 or 0.03 mg/kg eticlopride HCl), followed by MPH (5 mg/kg). Approximately 10 min after MPH administration, the rats were placed into the paired context for a 10-min trial. One day after conditioning on PD38, a preference test was administered with dividers removed. One day following the preference test on PD39, brain tissue was removed, and the nucleus accumbens and striatum were analyzed for BDNF. Results revealed that MPH conditioning resulted in an increased preference that was blocked by either dose of SCH-23390, but generally not affected by either dose of eticlopride. Further, the higher dose of SCH-23390 resulted in a conditioned place aversion in males, presumably due to an increased number of dopamine D1 receptors in adolescent males. MPH produced a significant increase of striatal and accumbal BDNF alleviated by SCH-23390 or eticlopride. These results show that MPH results in CPP in adolescent male and female rats and these effects appear to be mediated by the dopamine D1 receptor, but the effects of MPH on BDNF appear to be mediated by both dopamine receptor families.

In two experiments, we analyzed the effects of methylphenidate (MPH) on conditioned place preference (CPP) in adolescent male and female rats, and the effects of MPH on the dopamine transporter (DAT). In Experiment 1, male and female rats were conditioned for 5 consecutive days from postnatal day (P)44 to P48 with saline, 1, or 5 mg/kg MPH. On the post conditioning preference test, the group administered the 1 mg/kg dose of MPH resulted in no significant preference compared to controls, whereas the 5 mg/kg dose of MPH produced a robust significant preference for the paired context, but there were no sex differences. Analysis of the DAT revealed that animals conditioned with the 5 mg/kg dose of MPH demonstrated a significant decrease of the dopamine transporter (DAT) in the nucleus accumbens and striatum compared to controls. In Experiment 2, animals were conditioned using an every second day paradigm from P33–41 to model a previous MPH treatment regimen that had revealed sex differences in behavioral sensitization. MPH produced an increased preference for the paired context on a post-conditioning preference test in Experiment 2, but as in Experiment 1, no sex differences were observed. These data show that a relatively high dose of MPH has rewarding associative effects in both adolescent male and female rats reliably across two different conditioning paradigms and ages in adolescence, but no sex difference. In addition, MPH results in a significant decrease of the DAT in drug reward brain areas which has implications toward plasticity of the brain's reward system.