In order to gain further insight into the mechanism of contingent tolerance to amphetamine anorexia (Carlton & Wolgin, 1971), an attempt was made to determine the role of anorexia and behavioral activation (increased locomotion and/or stereotypy) in the initial suppression of feeding produced by the drug. Rats administered chronic injections of either saline or amphetamine (2 or 4 mg/kg) were given milk either directly into the mouth through an intraoral cannula or in a standard drinking tube. It was reasoned that although drug-induced anorexia would affect intake with both methods of feeding to the same degree, the disruptive effect of behavioral activation would be greater in bottle-fed rats. The results revealed that bottle-fed rats given amphetamine showed substantially greater suppression of intake than cannula-fed rats. Saline-treated rats showed almost identical milk intake with the two methods. Recovery of intake occurred in all drugged rats except those given 4 mg/kg and fed by bottle. In the tolerant groups, rats fed by bottle and given 2 mg/kg recovered at a faster rate than cannula-fed rats at either dose. These results demonstrate that in the normal drinking condition, the initial suppression of intake is caused by a combination of anorexia and behavioral interference and that tolerance occurs to both of these effects.
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.
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