Tolerance to Naloxone-Induced Suppression of Intake: Learning and Cross-Tolerance to Cholecystokinin in Rats

Experiments were conducted to evaluate the contribution of conditioning to tolerance to the meal-suppressive effect of naloxone (Nx) in rats. The results indicated (a) Nx suppresses consumption in a dose-dependent manner; (b) tolerance to this suppression of intake is "contingent" (the rat must eat in conjunction with drug administration for tolerance to develop); (c) tolerance is displayed only in the context of environmental cues previously associated with Nx; (d) Nx-tolerant rats overeat when presented with cues previously associated with the drug; (e) Nx-tolerant rats display cross-tolerance to cholecystokinin. The results are consistent with C.X. Poulos and H. Cappell's (1991) "homeostatic" theory of tolerance, as well as with the results of other experiments indicating that conditioning contributes to tolerance to many effects of various drugs.