Amphetamine tolerance and body weight set point: a dose-response analysis

The theory that amphetamine anorexia and tolerance reflect the lowering of a set point for body weight regulation was evaluated. In the first experiment, rats given either 2 or 4 mg/kg d-amphetamine and access to milk ultimately achieved comparable levels of tolerance and maintained their weight at 94%-96% of control levels. Thus, the level of maintained body weight was not dose-dependent. In the second experiment, increasing the doses resulted in renewed anorexia and weight loss, and the appearance of behavioral stereotypies. Whereas mean intake then recovered, body weight remained at 79%-82% of control levels. However, milk intake for individual rats was extremely variable. Such variability is inconsistent with the notion that body weight was actively regulated by caloric intake. Drug withdrawal had little further effect on intake, and it led to weight "rebound" in only one group. When subsequently retested with the original doses, both groups were again anorexic and showed more intense stereotypy. This finding suggests that drug withdrawal caused a general increase in sensitivity to amphetamine, rather than a set-point-related change in feeding. Taken together, the data do not support the set point theory of amphetamine tolerance.