Acute Effects of d-Amphetamine on the DRL Schedule Behavior in the Rat: Comparison with Selective Dopamine Receptor Antagonists

Abstract

Amphetamine and it analogs have been shown to affect operant behavior maintained on the\r\ndifferential reinforcement of a low-rate (DRL) schedule. The aim of the present study was to investigate\r\nwhat specific component of the DRL response is affected by d-amphetamine. The acute effects of\r\nd-amphetamine on a DRL task were compared with those of the selective dopamine D1\r\n and D2\r\n receptor\r\nantagonists, SCH23390 and raclopride, respectively. Pentylenetetrazole and ketamine were also used as\r\ntwo reference drugs for comparison with d-amphetamine as a psychostimulant. Rats were trained to\r\npress a lever for water reinforcement on a DRL 10-s schedule. Acute treatment of d-amphetamine\r\n(0, 0.5, and 1.0 mg/kg) significantly increased the response rate and decreased the reinforcement in a\r\ndose-related fashion. It also caused a horizontal leftward shift in the inter-response time (IRT)\r\ndistribution at the doses tested. Such a shifting effect was confirmed by a significant decrease in the peak\r\ntime, while the mean peak rate and burse response remained unaffected. In contrast, both SCH23390\r\n(0, 0.05, and 0.10 mg/kg) and raclopride (0, 0.2, and 0.4 mg/kg) significantly decreased the total, nonreinforced, and burst responses. The de-burst IRT distributions were flattened out as shown by the doserelated decreases in the mean peak rate for both dopamine antagonists, but no dramatic shift in peak\r\ntime was detected. Interestingly, neither pentylenetetrazole (0, 5, and 10 mg/kg) nor ketamine (0, 1, and\r\n10 mg/kg) disrupted the DRL behavioral performance. It is then conceivable that d-amphetamine at the\r\ndoses tested affects the temporal regulation of DRL behavior. The effectiveness of d-amphetamine is\r\nderived from its drug action as a psychostimulant. Taken together, these data suggest that different\r\nbehavioral components of DRL task are differentially sensitive to pharmacological manipulation.