Differential interaction of cholecystokinin with morphine and phencyclidine: Effects on operant behavior in pigeons

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To extend previous operant research in rats with morphine and cholecystokinin (CCK), these two substances were given alone and in combination to pigeons. In one component of a multiple schedule, responding of pigeons (key pecking) was reinforced under a fixed-ratio (FR 50) schedule of food presentation. In the other component, responding had no programmed consequence (timeout). Each session consisted of four 10-min timeout components alternating with four 5-min FR components. In Experiment 1, cumulative dose-effect curves for morphine were obtained by giving an IM injection before each of four FR components; successive injections increased the cumulative dose by 1 4 log-unit steps. In general, as the cumulative dose of morphine increased, the overall response rate in each FR component decreased. Dose-dependent decreases in response rate also occurred when single noncumulative doses of CCK were administered alone 20 min prior to the start of the session. This effect of CCK alone diminished as the session progressed. When CCK was given as a pretreatment before cumulative doses of morphine, the morphine dose-effect curve for response rate shifted to the left. At intermediate doses of CCK, the "potentiation" was so complete that two of three subjects failed to respond during any of the four FR components (i.e., the dose-effect curve for morphine had shifted approximately 1 log-unit to the left). In order to evaluate the pharmacological specificity of this effect, cumulative doses of phencyclidine were administered in combination with CCK (Experiment 2). Unlike the interaction between morphine and CCK, the interaction between phencyclidine and CCK was reciprocal. After pretreatment with each dose of CCK, high doses of phencyclidine tended to produce smaller rate-decreasing effects than those obtained with phencyclidine alone. Moreover, low doses of phencyclidine attenuated the rate-decreasing effects of the higher doses of CCK in the initial FR components. The results of Experiment 1 extend the generality of previous findings in rats with morphine and CCK on schedule-controlled behavior, while the results of Experiment 2 indicate distinct differences in the way in which CCK interacts with morphine and phencyclidine. © 1991.

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Pharmacology, Biochemistry and Behavior

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