Methylphenidate and d-amphetamine: effects and interactions with alphamethyltyrosine and tetrabenazine on DRL performance in rats.

Abstract

The effects of d-amphetamine and methylphenidate and their interactions with amine-depleting drugs were examined in rats trained to press a lever to obtain water reinforcement on a schedule that differentially reinforced responding at low rates (DRL). Both methylphenidate (2.5-20.0 mg/kg) and d-amphetamine (0.375-3.0 mg/kg) increased the rate of responding and decreased the frequency of reinforcement on the DRL schedule. Both drugs also shifted the interresponse time (IRT) distributions to the left such that the modal IRT occurred well below the minimum IRT required for reinforcement (d-amphetamine was abut eight times more potent than methylphenidate for each of these effects). The effects of both d-amphetamine and methylphenidate on DRL performance were attenuated by administration of alphamethyltyrosine (AMT) (150 mg/kg) and both drugs attenuated the response rate-suppressing effects of tetrabenazine (TBZ) (4.0 mg/kg). The similarity of the drug interactions between methylphenidate or amphetamine and AMT or TBZ suggest that the doses of methylphenidate and d-amphetamine examined act on similar catecholaminergic pools with the central nervous system to influence DRL performance.