Tolerance to amphetamine anorexia: role of learning versus body weight settling point

Three experiments were conducted to clarify the role of learning and body weight settling point in the development of tolerance to amphetamine anorexia. In the first experiment, rats that had become tolerant to the suppressant effect of amphetamine on milk intake were anorexic when subsequently offered other foods or water during a transfer test. These results appear to support a conditioning interpretation, which predicts a loss of tolerance when cues associated with drug administration are altered. Subsequent experiments examined the long-term effect of changing diets. In Experiments 2 and 3, rats made tolerant with milk as the diet showed prolonged anorexia when switched to Purina pellets or slightly bitter milk. However, when switched from pellets or adulterated milk to milk, tolerant rats were anorexic only 1 day and then ingested significantly more of the new diet. These results are inconsistent with a conditioning interpretation. Further analysis revealed that tolerant rats maintained their weight below the level of saline controls despite the recovery of food intake. Moreover, the level at which they maintained their weight varied with the palatability of the diet. These results suggest that amphetamine lowers the settling point for body weight and that tolerance does not develop to this effect (cf. Stunkard, 1981). From this perspective, the reinstatement of prolonged anorexia when apparently tolerant rats were switched to a less palatable diet can be understood as an attempt to attain a lower weight level.