Tolerance to the anti-avoidance properties of cholecystokinin-octapeptide.

Previous investigations have suggested a neuroleptic-like action of cholecystokinin-octapeptide (CCK8) on conditioned-avoidance behavior. This study was initiated to test tolerance to this effect. Rats were trained to avoid electric shock in a shuttle box under a free-operant (Sidman) avoidance paradigm. Each shuttle response postponed a 0.2 sec, 1 mA shock for 20 sec. If the rat failed to respond, shock was delivered every 5 sec until a response occurred. After avoidance training, half of the rats received two daily injections of CCK8 (0.320 mg/kg, IP) and half received saline for 7 days. Rats were then tested on the Sidman avoidance 1 min after receiving CCK8 (0.640 mg/kg, IP) or saline. CCK8 depressed avoidance responding if rats received saline for 7 days prior to the test. Rats pretreated with CCK8 for 7 days were not significantly affected by CCK8 during the avoidance test. Thus, repeated injections of CCK8 result in tolerance to its anti-avoidance properties.