Corticosterone treatment before puberty sensitizes the effect of oral methylphenidate on locomotor activity in preadolescence and produces differential effects in adulthood

Abstract

The first objective of this study was to examine the effects of early exposure to methylphenidate and then those of re-exposure in adulthood. The second was to analyze the effect of corticosterone treatment during pre-puberty on oral methylphenidate consumption and, consequently, the effect of this psychostimulant on locomotor activity in preadolescent and adult rats. Experiment 1: from 31 to 39 days of postnatal age (PA), Wistar rats were exposed to either oral methylphenidate or water. Experiment 2: from 24 to 39 days PA, the rats received either corticosterone (2.0 mg/kg/day/subject) or a saline solution. From 31 to 39 days PA, rats were exposed to either methylphenidate or water. During adulthood, all rats in experiments 1 and 2 were exposed to either methylphenidate or water, and subsequently exposed to a free-choice condition of the same two substances. Results: Experiment 1. Methylphenidate increased locomotor activity (LA) regardless of age. In adulthood, higher methylphenidate consumption was observed in the group that had not been exposed to this substance, compared to the early methylphenidate-exposed group. Experiment 2. Corticosterone did not affect methylphenidate consumption during preadolescence or adulthood; however, the LA induced by methylphenidate was higher in the preadolescents that had been treated with corticosterone + methylphenidate than in the animals treated only with methylphenidate. In adulthood, methylphenidate produced higher LA in the animals previously treated with corticosterone + methylphenidate than in those that had received previous treatment exclusively with corticosterone. These results suggest that preadolescent corticosterone exposure produced a sensitizing effect of methylphenidate on LA in preadolescence. The differential effect on LA in adulthood depended on whether the corticosterone was administered with or without methylphenidate in preadolescence, which would suggest an enduring effect of the early synergic action between these two substances.