Effects of acute and chronic cocaine on milk intake, body weight, and activity in bottle and cannula-fed rats

The effects of cocaine on the milk intake, body weight and activity of bottle- and cannula-fed rats was compared under both acute and chronic dosing conditions. Bottle-fed rats were initially more hypophagic than cannula-fed rats when given acute injections of cocaine (4–40 mg/kg). Following chronic injections of the drug (16 mg/kg), bottle-fed rats developed tolerance, as shown by a rightward shift in the dose-response function for milk intake. Such tolerance was accompanied by a decrease in drug-induced motor activity. In contrast, cannula-fed rats showed marked sensitization of stereotyped movements. Bottle-fed rats showed marked sensitization of stereotyped movements. However, weight loss per se was not a determining factor in tolerance development, because cannula-fed rats given chronic injections of 32 mg/kg cocaine lost even more weight, but did not become tolerant. These results suggest that, at moderate doses, cocaine suppresses feeding primarily by inducing behaviors that are incompatible with the appetitive phase of feeding, and that tolerance involves learning to inhibit such responses in order to feed.