Methylphenidate Conditioned Place Preference in Adolescent Male and Female Rats

Methylphenidate (MPH) is a psychostimulant drug that is commonly prescribed for Attention Deficit-Hyperactivity Disorder (ADHD), however, this drug is also abused. The primary pharmacological action of MPH is similar to that of cocaine, in that the drug blocks the dopamine transporter and enhances dopamine neurotransmission. The similarity to cocaine has brought to light legitimate concerns at the abuse liability of MPH. The focus of the present study was to analyze MPH conditioned place preference (CPP) in adolescent rats, with the focus on sex differences in this effect. CPP is a commonly used measure of drug reward in rats. Animals were also tested at two different time periods, from postnatal day (P)32-38 or P43-49, representing periods during adolescence both before and after the commencement of the estrous cycle in females, which begins on approximately P41. After an initial preference test on P32 or 43 revealed no significant preference for either context, an unbiased procedure was used. Beginning on P33 or P44, MPH (5 mg/kg) was paired with either context in animals in the drug condition, balanced across males and females. Controls were given saline in both contexts (N=8-9 in all groups). A preference test was given on P38 or P49 with dividers removed. Results revealed no sex or age difference, but MPH induced a robust increased preference for the paired context in both males and females on the post-conditioning preference test, which was significantly greater than male and female controls. Interestingly, males demonstrated significantly higher levels of activity and a higher number of entries made into the paired context when tested at the younger age, but there were no sex differences in these responses in older animals. Brain tissue is currently being analyzed for levels of the dopamine transporter (DAT), and this data will be presented. Past studies have shown that females have a higher number of DAT in the striatum compared to males in adulthood, but this has never been established in adolescence. In conclusion, it appears that a 5 mg/kg dose of MPH is capable of inducing drug reward in adolescent rats, and unlike recent results from our laboratory regarding behavioral sensitization, there are no sex differences in this response