Research articleChronic methylphenidate regulates genes and proteins mediating neuroplasticity in the juvenile rat brain

- Chronic methylphenidate upregulated Arc, IRSp53, Cdc42 and Arp2 expression in cerebral areas associated with reward, cognition and addiction.
- Arc and IRSp53 were down-regulated in the cerebellum following chronic methylphenidate administration.
- The IRSp53 pathway should to be studied further to establish its role in methylphenidate induced neuronal plasticity and long term behavioural effects.

Methylphenidate (MPH) is the front-line psychostimulant medication prescribed for alleviating the symptoms associated with attention deficit hyperactivity disorder (ADHD) in children. Here, we investigated the effects of chronic MPH (2.0 mg/kg, twice daily for 15 days) exposure to young rats (20-25 days old at start of treatment) on the expression of genes and proteins associated with neuroplasticity, such as activity regulated cytoskeleton-associated protein (Arc), insulin receptor substrate protein 53 (IRSp53), cell division control protein 42 (Cdc42), and actin-related protein 2 (Arp2). Chronic MPH increased Arc expression in areas of the cerebrum including, the striatum, nucleus accumbens and hippocampus. In addition, chronic MPH also increased the expression of IRSp53 in the striatum, while Cdc42 and Arp2 were specifically increased in the nucleus accumbens. Conversely, chronic MPH decreased Arc and IRSp53 protein expression in the cerebellum, indicating differential effects of the drug in cerebral areas relative to the cerebellum. Overall, our results indicate that chronic MPH treatment increases expression of genes and proteins associated with dendritic spine formation and neuronal plasticity in target areas of the cerebrum while it decreases the expression in the cerebellum.