Research reportAge and genetic strain differences in response to chronic methylphenidate administration

Methylphenidate hydrochloride (MPD) is a psychostimulant used in the treatment of attention deficit hyperactive disorder (ADHD) in adolescents and adults alike. Adolescence involves a period of neural development that is highly susceptible to environmental and pharmacological influence. Exposure to a psychostimulant like MPD during this crucial time period may cause permanent changes in neuronal function and formation. Another factor that may influence changes in neuronal function and formation is genetic variability. It has been reported that genetic variability affects both the initial behavioral response to drugs in general and psychostimulants in particular, and subsequently whether tolerance or sensitization is induced. The objective of the present study is to investigate the dose-response effects of repeated MPD administration (0.6, 2.5, or 10.0 mg/kg, i.p.) using an open field assay to investigate if there are differences between adolescent and adult Wistar-Kyoto (WKY), Spontaneously Hyperactive rat (SHR), and Sprague-Dawley (SD) rats, respectively, and if the genetic variability between the strains influences the degree of change in locomotion. The acute and chronic administration of MPD resulted in unique differences in the level of increasing intensity in locomotor activity in each rat strain, with adult rats for the most part having a more intense increase in locomotor activity when compared to their adolescent counterparts. In conclusion, significant response differences among rat strains and age to acute and chronic MPD administration were observed only following the 2.5 and 10.0 mg/kg i.p. doses and not following the lower MPD dose (0.6 mg//kg i.p.). In addition the variability in activity among the rat strain and age suggests that MPD may affect the same neuronal circuit differently in each strain and age. The unique differences among the individual locomotor indices suggest also that each locomotor index is regulated by different neuronal circuits, and each affected differently by MPD.

Research highlights▶ Age plays major role in animal's response to methylphenidate. ▶ Genotype plays major role in animal's response to methylphenidate. ▶ Each age exhibits different dose response characteristics. ▶ Each genotype exhibits different dose response characteristics. ▶ The highest dose of MPD elicits similar effects in all the groups.