Dopamine Receptor Antagonists Reverse Amphetamine-Induced Behavioral Alteration on a Differential Reinforcement for Low-rate (DRL) Operant Task in the Rat

Abstract

Previous studies have shown that amphetamine significantly alters operant responding on the\r\nbehavior maintained on a schedule of differential reinforcement of low-rate (DRL). As such, behavioral\r\ndeficiency of DRL responding has been observed by the drug-induced increase of non-reinforced\r\nresponses and a leftward shift of inter-response time (IRT) curve on DRL responding in the rat.\r\nHowever, the neurochemical basis for amphetamine-induced DRL behavioral alternations remain to be\r\nelucidated. The present study was then designed to examine whether the effects of amphetamine were\r\ndependent on dopamine-subtyped receptors, this was carried out by the co-administration of the\r\nselective D1 and D2 receptor antagonists, SCH23390 and raclopride respectively. Rats were first trained\r\nto perform on DRL 10-sec task and then divided into four groups, which received separate types of\r\ndouble injections before the behavioral session. The four groups were the saline control group, the\r\namphetamine alone group, the dopamine antagonist alone group, and the combination amphetamine and\r\ndopamine antagonist group. The saline control group performed DRL responding in an efficient manner\r\nwith a major index for the peak time of the IRT curve, which was fairly localized within the 10-sec bin\r\nthroughout the test phase. The subjects injected with amphetamine (1 mg/kg) significantly shortened\r\nIRT that led to a leftward shift of IRT curve, which was further revealed by a decreased peak time\r\nwithout significant effectiveness on the peak rate and burst response. Even though the group given\r\nSCH23390 or raclopride alone showed profound disruption on DRL behavior by flattening the IRT\r\ncurve, the co-administration of amphetamine with SCH23390 or raclopride reversed the aforementioned\r\namphetamine-induced behavioral deficiency on DRL task. Together, these results suggest that the\r\ndopamine D1 and D2 receptors are involved and important to the temporal regulation of DRL response\r\nunder psychostimulant drug treatment. Furthermore, this highlights the involvement of the brain\r\ndopamine systems in the temporal regulation of DRL behavior performance.