An assessment of the interaction between cholecystokinin and the opiates within a drug discrimination procedure

Cholecystokinin (CCK) has been reported to antagonize a variety of opiate-induced effects, including nociception, body shaking, thermoregulation and locomotion. Consistent with these results, a number of CCK antagonists potentiate the opiates in a range of behavioral and physiological assessments. The present study examined the interaction between CCK and the opiates within the conditioned taste aversion baseline of drug discrimination, a design that utilizes the stimulus properties of a drug to control behavior. Within this baseline, animals acquired a CCK/vehicle discrimination, drinking different levels of saccharin following the administration of CCK and the CCK vehicle. Morphine blocked, whereas naloxone (mu receptor antagonist) and MR 2266 (kappa receptor antagonist) potentiated, the stimulus properties of CCK, although discriminative control by CCK did not generalize to either naloxone or MR 2266 when administered alone. These data are thus consistent with a physiological (rather than a pharmacological) interaction between CCK and the opiates, mediated by way of mu and kappa opiate receptor subtypes. The possible underlying basis for the interaction between CCK and the opiates is discussed, as is the opiate and CCK receptor subtype mediation of the aforementioned effects.