THE EFFECTS OF d- AND l- AMPHETAMINE ON FIXED-INTERVAL AND FIXED-RATIO BEHAVIOR IN TOLERANT AND NONTOLERANT RATS

¹ Departments of Pharmacology and Psychiatry, University of Minnesota, Minneapolis, Minnesota

Male, albino rats were trained to press a lever for food pellets on a fixed-interval (FI) 75-second or a fixed-ratio (FR) 30 schedule of reinforcement. The dose-related effects of d- or l-amphetamine on responding during successive 15-second segments of the FI 75-second interval, as well as the overall response rate, were investigated. The i.p. injection of 0.16 mg/kg of d-amphetamine increased responding significantly in the first 15 seconds and last 30 seconds of the 75-second interval, while the dose of 0.50 mg/kg affected responding significantly throughout the interval. Both of these doses of d-amphetamine increased overall FI responding significantly. The highest dose of d-amphetamine used (1.0 mg/kg) increased responding in the first 30 seconds of the interval, while decreasing responding in the last 15 seconds. The overall response rate was not altered significantly by 1.0 mg/kg of d-amphetamine. FI responding was not affected by lower doses of l-amphetamine (0.15 and 0.30 mg/kg), whereas more intermediate doses (0.50 and 1.0 mg/kg) tended to increase responding in the last 15 to 45 seconds of the interval. Overall response rates were likewise increased. Responding in the first 15-second segment was not affected by most doses of l-amphetamine (0.15-1.0 mg/kg), but 1.5 mg/kg decreased responding in this segment while not affecting responding in the subsequent segments of the interval or overall responding. The highest dose of l-amphetamine investigated (2.0 mg/kg) decreased responding in the first 15-second segment and in the last 30 seconds of the interval. Overall responding was also decreased by this dose of l-amphetamine. Repeated daily administration of d- and l-amphetamine resulted in a gradual decline in the effectiveness of the drugs to alter schedule-controlled responding. A complete cross-tolerance was not observed between d- and l-amphetamine at doses which were approximately equieffective in altering FI 75-second (0.16 and 0.50 mg/kg, respectively) or FR 30 performance (1.0 and 4.0 mg/kg, respectively). The lack of a complete cross-tolerance using either schedule of reinforcement suggests that d- and l-amphetamine are producing unequal peripheral and/or central effects at the doses employed, and therefore may be affecting schedule-controlled behavior by different mechanisms of action.