Abstract

Repeated exposure to psychostimulants activates mesocorticolimbic dopamine (DA), resulting in an increased locomotor response to the same dose of drug, known as sensitization. Research has yet to establish whether locomotor sensitization differs based on the age when a stimulant treatment is administered. Netrin-1 is a guidance cue in the brain that has been implicated in stimulant-induced locomotor sensitization. Netrin-1 receptors, deleted in colorectal cancer (DCC) and UNC-5, are expressed throughout the mesocorticolimbic system, and repeated amphetamine (AMPH) treatment alters levels of these receptors in the ventral tegmental area (VTA) in an age-dependent manner. To investigate whether methylphenidate (MPH) treatment induces locomotor sensitization and changes in Netrin-1 receptor expression differentially across development, prepubescent and adult rats were administered MPH (2mg/kg) or saline twice daily, for 10 days. One or 4 weeks after treatment ended, rats were administered a dose of cocaine (COC; 10mg/kg) and sensitization was assessed. DCC and UNC-5 levels in the VTA were evaluated through Western blots. The results show that prepubescent rats tested 4 weeks after MPH treatment exhibit significant locomotor sensitization compared to saline controls. However, adults treated with MPH and tested 1 or 4 weeks after treatment, and prepubescent rats tested 1 week after treatment, did not exhibit sensitization. MPH treated rats from both age groups had no significant differences in DCC or UNC-5 expression in the VTA compared to saline controls. These findings indicate prepubescent MPH treatment induces locomotor sensitization, a behaviour that does not require changes in Netrin-1 receptor expression