Age and sex differences in the locomotor effect of repeated methylphenidate in rats classified as high or low novelty responders

Rationale Rats displaying high levels of activity in an inescapable novel environment (high responders; HR) are more sensitive to the locomotor effect of stimulant drugs than rats displaying low levels of activity (low responders; LR).Objective The current study determined the age- and sex-dependent locomotor effects of repeated methylphenidate in HR and LR rats.Materials and methods Periadolescent and adult male and female Sprague–Dawley rats were first classified as HR or LR; rats were also classified as high or low novelty seekers based on free-choice preference for a novel environment. Locomotor activity was subsequently assessed after ten daily injections of methylphenidate (3 or 10 mg/kg s.c.) or saline. Fifteen days later, rats were challenged with saline and methylphenidate (10 mg/kg) over 2 days.Results During the repeated methylphenidate treatment phase, adult females showed greater methylphenidate-induced hyperactivity than adult males; there was no reliable difference in methylphenidate-induced hyperactivity between HR and LR rats of either age or sex. However, periadolescent male HR rats given repeated methylphenidate showed greater conditioned hyperactivity after the saline challenge than periadolescent male LR rats. Further, adult female HR rats given repeated methylphenidate showed greater conditioned hyperactivity and sensitization than adult female LR rats. In contrast, although free-choice novelty preference was greater among periadolescents than adults, individual differences in this variable did not predict the effect of repeated methylphenidate during any phase of the experiment.Conclusion Although individual differences in response to inescapable novelty predict methylphenidate-induced conditioned hyperactivity and sensitization, this relationship is moderated by age and sex.