Prior drug experience and effects of amphetamine on schedule controlled behavior

Food deprived rats were trained to lever press for food pellets on a fixed ratio 40 schedule of reinforcement. Following 18 days of training, rats received d-amphetamine IP (1.0 mg/kg) as a drug control. Three days later, half of the animals were given d-amphetamine and half were given NaCl for six days. Tolerance to the disruptive effects of d-amphetamine on FR responding was not noted in the drugged group. Both groups received 14 more daily sessions with NaCl followed by 12 additional days of drug. Rats with previous drug experience exhibited tolerance in 6 days, while the other group required 12 days. In a second study, rats were trained to respond on an unsignalled continuous avoidance schedule for 8–10 weeks. Two groups of rats were given 7 daily drug sessions in which d-amphetamine (1.0 mg/kg) was administered IP. Each drug session was followed by 2 daily NaCl control sessions. In the first 3 drug sessions of one group, d-amphetamine was injected IP 30 min after the end of the session. All other injections were given immediately before placement into the operant chamber. During the first session in which the drug was injected before placement into the chamber, response increases were significantly higher in rats with drug experience outside the behavioral situation than in drug naive subjects. These studies emphasize the importance of prior drug exposure when investigating behavioral effects of drugs.