This study was designed to determine if tolerance to cholecystokinin octapeptide (CCK8) could be prevented or minimized by spacing injections, and if an appetitive operant conditioning paradigm provides a sensitive baseline to test the effects of CCK8. Male Sprague-Dawley rats were trained to press a lever for water according to a fixed-interval 60-sec schedule of reinforcement. After response rate stabilized, rats were given a series of CCK8 (0.04 mg/kg, ip) injections spaced several days apart. The first injection of CCK8 produced complete response suppression during the 30-min test session, while later injections produced partial or complete suppression. Thus, tolerance to CCK8, as measured by operant response rate, may be minimized if injections are appropriately spaced.
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