A comparison of peripheral and central effects of CCK8 on water-reinforced operant responding

Systemic administration of cholecystokinin-octapeptide (CCK8) suppresses operant responding in water deprived rats, but it is unclear whether this effect is centrally or peripherally mediated. Rats were trained to press a lever for water in an operant conditioning chamber under a variable-interval schedule of reinforcement. After response rate stabilized injections were administered, and response suppression was measured by comparing injection response rate to baseline rate. Intracerebroventricular injections of CCK8 reduced lever pressing at relatively high doses (20 and 50 micrograms/rat). But in a direct comparison, the same dose of CCK8 (20 micrograms/rat) given intraperitoneally reduced responding significantly more than when given into the lateral ventricle. The suppressive effects of CCK8 (30 and 300 micrograms/kg i.p.) were significantly reduced by complete abdominal vagotomy. The effects of CCK8 (30 micrograms/kg i.p.) were blocked by pretreatment with the specific competitive CCK8 antagonist dibutyryl cyclic GMP (70 and 140 mg/kg i.p.), but not by the acetylcholine antagonist atropine (0.1 to 10 mg/kg i.p.). These data suggest that suppression by CCK8 of operant lever pressing in water-deprived rats is primarily mediated by vagal afferent fibers.