Tolerance pattern of the anorexigenic action of amphetamine in rats

1. When food intake in fasted male rats was recorded daily for two consecutive 2 h periods it revealed a characteristic pattern.2. In the control rats the food intake was greater during the first than the second 2 h period. Following (+/-)-amphetamine 5 mg/kg s.c. 30 min before food for 7 days there was a reversal of this normal food pattern. The rats consumed much less during the first 2 h period but progressively more during the second 2 h period.3. The first 2 h food intake remained low throughout the treatment period and there was no evidence of development of tolerance despite continuation of treatment.4. The second 2 h food intake steadily increased, contributing to the appearance of tolerance when only total 4 h food intake was recorded.5. On withdrawal of amphetamine, there was immediate recovery of the first 2 h food intake. The second 2 h food intake, though decreased, remained high compared to the pretreatment level and may be responsible for the production of the ;rebound' phenomenon following withdrawal of amphetamine.