Age-related distribution of c-fos expression in the striatum of CD-1 mice after acute methylphenidate administration

Abstract

Ritalin (methylphenidate hydrochloride, MPH) is the drug of choice for the treatment of attention deficit hyperactivity disorder. Previous research has shown that MPH administration affects the adult brain in a manner different from the young brain. In the current study, we set out to determine the target brain regions of acutely administered MPH at different stages of development. On postnatal days 3, 7, 11, 24, and 45, mice were treated with a single injection (s.c.) of saline, 5 or 20 mg/kg of MPH, and sacrificed 1 h later. Localization of c-fos expression was determined by immunocytochemistry. Compared to saline treated controls, mice treated with the high dose of MPH (20 mg/kg) showed dense Fos-immunoreactivity (Fos-IR) in the striatum. In most cases the low dose of MPH (5 mg/kg) produced only weak c-fos expression that was nearly indistinguishable from saline-treated controls. At PND 3 and 7, Fos-IR was localized in patches in the striatum. This patchy distribution of c-fos positive cells began to decline by PND 11 and was absent in PND 45 mice, with Fos-IR showing a scattered distribution throughout the striatum. The results of this study indicate that MPH induces the expression of c-fos in the same brain regions as cocaine and amphetamine, and that this expression is distributed differentially according to the age of the mouse.