Restoration of Cdk5, TrkB and Soluble N-ethylmaleimide-Sensitive Factor Attachment Protein Receptor Proteins after Chronic Methylphenidate Treatment in Spontaneous Hypertensive Rats, a Model for Attention-Deficit Hyperactivity Disorder.

Objective: Synaptic vesicle mobilization and neurite outgrowth regulation molecules were examined in modulation of effects of methylphenidate (MPH) in Spontaneous Hypertensive Rats (SHRs), a model for attention-deficit hyperactivity disorder (ADHD).

Methods: We compared the changes in the protein expression level of Cyclin dependent kinase 5 (Cdk5) and molecular substrates of Cdk5; tropomyosin receptor kinase B (TrkB), syntaxin 1A (STX1A) and synaptosomal-associated protein 25 (SNAP25). Comparisons were made in prefrontal cortex of vehicle (distilled water i.p. for 7 days)-treated SHRs, vehicle-treated Wistar Kyoto Rats (WKYs) and MPH (2 mg/kg i.p. for 7 days) treated SHRs.

Results: The Cdk5 level of vehicle-treated SHRs was significantly decreased compared to the Cdk5 level of vehicle-treated WKY rats, but was restored to the expression level of vehicle-treated WKYs in MPH-treated SHR. The ratio of p25/p35 was significantly decreased in MPH-treated SHR compared to vehicle-treated SHR. Moreover, TrkB, STX1A and SNAP25 of vehicle-treated SHRs were significantly decreased compared to vehicle-treated WKY rats, but were restored to the expression level of vehicle-treated WKYs in MPH-treated SHR.

Conclusion: The results show that Cdk5, TrkB, STX1A, and SNAP25 were involved in the modulation of MPH effects in prefrontal cortex of SHRs and play important role in treatment of ADHD.