Rewarding properties of methylphenidate: Sensitization by prior exposure to the drug and effects of dopamine D1-and D2-receptor antagonists

In drug addiction, a sensitization phenomenon has been postulated to play a critical role. The aim of our study was to evaluate whether sensitization occurs to the rewarding properties of methylphenidate, a psychostimulant dr ug known to possess abuse potential, as assessed with the biased conditione d place preference method in rats. In addition, since the brain dopaminergi c system is considered to be important in drug-reward, the involvement of d opamine D1- and D2-receptors both in the rewarding properties of methylphen idate and in sensitization to these properties was assessed. Conditioning w ith methylphenidate at doses of 1.25 to 20 mg/kg increased preference for t he paired environment, whereas a dose of 0.31 mg/kg was ineffective. Howeve r, following the 7-day sensitization treatment with methylphenidate (0.62-2 0 mg/kg), conditioning with a dose of 0.31 mg/kg resulted in an increased p reference for the paired environment, i.e., the rewarding properties of met hylphenidate appeared to be sensitized. Control experiments indicated that the enhancement of preference was not due to attenuation of sensitization t reatment-induced withdrawal nor to tolerance to aversive properties of meth ylphenidate. When conditioned with methylphenidate, D1-antagonist SCH 23390 but not D2-antagonist raclopride prevented place preference. However, when coadministered with methylphenidate during the sensitization treatment, bo th SCH 23390 and raclopride prevented the development of sensitization. The se data indicate that the rewarding properties of methylphenidate are sensi tized by prior exposure to the drug and that both D1- and D2-receptors, the latter of which possibly more specifically, appear to be involved in the d evelopment of this sensitization.