Cholecystokinin potentiates the rate-decreasing effects of morphine on schedule-controlled behavior in rats

In one component of a multiple schedule, responding (licking in rats) was reinforced under a fixed-ratio (FR 50) schedule of water presentation. In the other component, responding had no programmed consequences (timeout). Each session consisted of four 10-min timeout components alternating with four FR components. In general, increasing cumulative doses of morphine (3.2-18 mg/kg) produced a dose-dependent decrease in the overall rate of responding. In one subject, cholecystokinin (CCK) alone (10-32 micrograms/kg) produced dose-dependent decreases in rate in the first component, while in the other two subjects relatively little decrease in rate occurred. When these doses of CCK were given as a pretreatment before morphine, the decrease in overall response rate was greater than that found with morphine alone. This interaction was most noticeable at the lowest dose of morphine where CCK produced a dose-dependent "potentiation" of the rate-decreasing effects. Although the potentiation of CCK was not as evident at the intermediate doses of morphine, there were instances in which the rate-decreasing effects produced by the combination were greater than those expected from addition of the effects of CCK and morphine alone. In contrast, when naltrexone (1 mg/kg) was given as a pretreatment, little or no rate-decreasing effects were produced by the cumulative doses of morphine. Furthermore, pretreatment with naltrexone and the administration of a higher dose range of morphine indicated the dose-effect curve for morphine had shifted approximately 3/4 log-units to the right.(ABSTRACT TRUNCATED AT 250 WORDS)