Neuroleptic-like properties of cholecystokinin analogs: Distinctive mechanisms underlying similar behavioral profiles depending on the route of administration

Abstract

Rats were trained to discriminate vehicle injections from intraperitoneal injections of 3 μg/kg caerulein, a cholecystokinin (CCK) neuropeptide analog. The reward that reinforced correct choices was an electrical brain stimulation self-administered by bar pressing. Dose-response quantitative generalization was obtained by using 1 and 2 μg/kg caerulein. Qualitative generalization to the vehicle occurred after injecting 10, 20 and 200 μg/kg unsulfated CCK-8, 10, 20 and 200 μg/kg CCK-4, 5 μg/kg CCK-8 and 1 μg/kg caerulein, neurotensin or bombesin and 200 μg/kg apomorphine or 320 μg/kg amphetamine. Total generalization to the caerulein cue was obtained with 20 μg/kg sulfated CCK-8 or gastrin 2–17, 25 μg/kg somatostatin, 50 μg/kg haloperidol and 2 mg/kg chlorpromazine. The previous 5 mg/kg injection of an antiemetic drug such as chlorhydrate of trimethobenzamide did not eliminate the discriminative properties of a subsequent injection of caerulein. Our data thus tend to show that IP injection of caerulein produces effects similar to those of IP neuroleptics.