Treatment of ADHD with methylphenidate may sensitize brain substrates of desire

Aims. Currently, methylphenidate (MPH, trade name Ritalin) is the most widely prescribed medication for attention deficit/hyperactivity disorder (ADHD). We examined the ability of repeated MPH administration to produce a sensitized appetitive eagerness type response in laboratory rats, as indexed by 50-kHz ultrasonic vocalizations (50-kHz USVs). We also examined the ability of MPH to reduce play behavior in rats which may be partially implicated in the clinical efficacy of MPH in ADHD. Design. 56 adolescent rats received injections of either 5.0 mg/kg MPH, or vehicle each day for 8 consecutive days, and a week later received a challenge injection of either MPH or vehicle. Measurements. Both play behavior (pins) and 50-kHz USVs were recorded after each drug or vehicle administration. Results. MPH challenge produced a substantial 73% reduction in play behavior during the initial treatment phase, and during the last test (1 week post drug), 50-kHz USVs were elevated approximately threefold only in animals with previous MPH experience. Conclusions. These data suggest that MPH treatment may lead to psychostimulant sensitization in young animals, perhaps by increasing future drug-seeking tendencies due to an elevated eagerness for positive incentives. Further, we hypothesize that MPH may be reducing ADHD symptoms, in part, by blocking playful tendencies, whose neuro-maturational and psychological functions remain to be adequately characterized.