The Effects of Adolescent Methylphenidate Exposure on the Behavioral and Brain-Derived Neurotrophic Factor Response to Nicotine

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This study analyzed the interaction of adolescent methylphenidate on the behavioral response to nicotine and the effects of these drug treatments on brain-derived neurotrophic factor in the nucleus accumbens and hippocampus in male and female Sprague-Dawley rats. Animals were intraperitoneal administered 1 mg/kg methylphenidate or saline using a “school day” regimen (five days on, two days off) beginning on postnatal day (P)28 and throughout behavioral testing. In Experiment 1, animals were intraperitoneal administered 0.5 mg/kg (free base) nicotine or saline every second day for 10 days from P45–P63 and tested after a three-day drug washout on the forced swim stress task on P67–P68. Results revealed that adolescent methylphenidate blunted nicotine behavioral sensitization. However, methylphenidate-treated rats given saline during sensitization demonstrated decreased latency to immobility and increased immobility time on the forced swim stress task in males that was reduced by nicotine. In Experiment 2, a different set of animals were conditioned to nicotine (0.6 mg/kg free base) or saline using the conditioned place preference behavioral paradigm from P44–P51, and given a preference test on P52. On P53, the nucleus accumbens and hippocampus were analyzed for brain-derived neurotrophic factor. Methylphenidate enhanced nicotine-conditioned place preference in females and nicotine produced conditioned place preference in males and females pre-exposed to saline in adolescence. In addition, methylphenidate and nicotine increased nucleus accumbens brain-derived neurotrophic factor in females and methylphenidate enhanced hippocampus brain-derived neurotrophic factor in males and females. Methylphenidate adolescent exposure using a clinically relevant dose and regimen results in changes in the behavioral and brain-derived neurotrophic factor responses to nicotine in adolescence that are sex-dependent.