D-amphetamine has been shown to produce the leftward shift of response distribution on the differential reinforcement of low rate (DRL) behavioral performance, which drug effects are interpreted by an increase in clock speed on the timing task. However, little is known about the neural substrates underlying this drug-behavior interaction. The present study investigated the possibility of dopamine D1 and D2 receptors in the medial prefrontal cortex (mPFC) involved in modulating the alteration of timing regulation on DRL behavior induced by d-amphetamine. Water-deprived rats were trained to press lever on the reinforcement contingency of DRL 10-sec. For the drug treatment, d-amphetamine (1 mg/kg) was injected via IP route, whereas the selective D1 and D2 receptor antagonists (SCH23390 and reclopride, respectively) were locally infused into the mPFC in the doses of 3 and 30 nmole. D-amphetamine given alone significantly increased the total responses and decreased the reinforcers earned. The peak time of the inter-response times distribution was significantly decreased by d-amphetamine. Either SCH23390 or reclopride reversed the gross deficits of DRL responding induced by d-amphetamine. However, SCH23390, but not reclopride, at the higher dose reversed the peak time shortened by d-amphetamine. These data confirm that d-amphetamine can disrupt the timing regulation of DRL behavior by increasing the clock speed. Furthermore, blockade of dopamine D1 receptors in the mPFC are involved in reversing such behavior alteration.
Society for Neuroscience, Society for Neuroscience