This study was designed to analyze the effects of adolescent exposure to methylphenidate (MPH; trade name: Ritalin) on nicotine self-administration, the motivation to obtain nicotine, and accumbal neuronal firing rate in female adolescent rats. MPH is the most commonly prescribed medication for Attention Deficit-Hyperactivity Disorder (ADHD) which is diagnosed in 3-5% of adolescents in the United States. However, this disorder is often misdiagnosed, and MPH is often prescribed to individuals not diagnosed with ADHD. Adolescent female Sprague-dawley rats were ip administered 1 mg/kg MPH or saline using a “school day” regimen of five days on, two days off, beginning on postnatal day (P)28 and this regimen was maintained throughout testing. A 1 mg/kg dose of MPH has been shown to result in brain plasma levels equivalent to clinical dosing in humans. Indwelling catheters were implanted in the jugular vein at P35, and one week later on P42, animals began nicotine self-administration. MPH (1 mg/kg) was administered each day approximately 6 h before each self-administration session began, which allows for nearly full plasma clearance of MPH (half-life = 1 h) before self-administration commenced. Rats were reduced to 85% of their free-feeding body weight and sipper tubes were made available to the rats in this paradigm, and responses to licking the tube produced an infusion of nicotine solution (15μg/kg) over a range of fixed ratio (FR) reinforcement schedules followed by a progressive ratio (PR) schedule, a measure of motivation. The schedule of reinforcement during 60 min sessions was increased from an FR5 to FR15 over approximately a three-week period. Results revealed that MPH pre-exposed rats self-administered significantly higher amounts of nicotine as compared to animals treated with saline throughout the FR5 and FR10 schedules. Further, MPH enhanced the motivation to self-administer nicotine on the PR schedule compared to controls, demonstrating an enhanced motivation to obtain nicotine produced by MPH. Finally, animals that had been pre-exposed to MPH and self-administered nicotine demonstrated a lower rate of basal accumbal firing as compared to controls, but a burst firing in response to nicotine that was higher than rats pre-exposed to saline. In conclusion, MPH altered the behavioral and neural response to nicotine in the nucleus accumbens.

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.

In this study marital status and the alcoholism or non-alcoholism of the spouse are hypothesized to be important factors affecting the female alcoholic's personality and treatability.

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