Adolescent Methylphenidate Exposure Increases the Reinforcement Enhancing Effects of Nicotine

Methylphenidate (MPH) is widely prescribed during childhood and adolescence for treatment of attention deficit and hyperactivity disorder. MPH is also one of the most commonly abused prescription drugs. However, the effects of MPH exposure and MPH abuse on incentive motivation are not well known. Moreover, MPH abuse during adolescence could increase sensitivity to the incentive motivational effects of other abused drugs such as nicotine in adulthood. Thus, the goals of this experiment were to investigate the effects of MPH exposure on the motivation to obtain sucrose during adolescence and to examine whether adolescent methylphenidate exposure altered the incentive motivational effects of nicotine (NIC) in adulthood. Incentive motivation was measured using an operant conditioning paradigm with sucrose available under a progressive ratio schedule of reinforcement (PR). Adolescent female rats were used because our previous studies have shown stronger sensitization to the locomotor stimulant effects of MPH. Rats arrived at post-natal day 21 (P21) and were shaped to respond for sucrose (20% w/v) on the PR schedule beginning on P24. After stable operant responding was established, rats were randomly assigned to receive either MPH (n=7) or SAL (n=6) injections (intraperitoneal) 30 min prior to test sessions, with the constraint that sucrose rewards earned did not differ between groups. Injection tests began on P36 and were carried out on alternating days for 10 total tests (P36-54). Although there was a trend for increased motivation for sucrose in the MPH group, it did not reach statistical significance. No further testing occurred until the rats reached adulthood (P55-P78). Over the next 5 days (P79-P84), all rats were pretreated with subcutaneous NIC injections (0.4 mg/kg base) 15 min before testing sessions. Following this initial ‘sensitization’ period, rats were tested with different NIC doses (0-1 mg/kg base) from P85-P92. During the sensitization period, NIC increased responding equally in both groups. However, during the dose-response testing, rats in the MPH group were more sensitive to the incentive motivational effects of NIC - the median effective dose was significantly lower for rats exposed to MPH in adolescence. The findings suggest that MPH may have limited reinforcement enhancing effects in adolescents. However, exposure to MPH during adolescents may increase the incentive motivational effects of NIC in adulthood.