Neuroleptic-like properties of cholecystokinin analogs: distinctive mechanisms underlying similar behavioral profiles depending on the route of administration.
Rats were trained to discriminate vehicle injections from intraperitoneal injections of 3 micrograms/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 micrograms/kg caerulein. Qualitative generalization to the vehicle occurred after injecting 10, 20 and 200 micrograms/kg unsulfated CCK-8, 10, 20 and 200 micrograms/kg CCK-4, 5 micrograms/kg CCK-8 and 1 microgram/kg caerulein, neurotensin or bombesin and 200 micrograms/kg apomorphine or 320 micrograms/kg amphetamine. Total generalization to the caerulein cue was obtained with 20 micrograms/kg sulfated CCK-8 or gastrin 2-17, 25 micrograms/kg somatostatin, 50 micrograms/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.
De Witte
P
P
Laboratorie de Psychobiologie, Université de Louvain, Louvain-la-Neuve, Belgique.
Gewiss
M
M
Roques
B
B
Vanderhaeghen
J J
JJ
D000818:Animals; D014150:Antipsychotic Agents; D001058:Apomorphine / Q000494:pharmacology; D001921:Brain / Q000502:physiology; D002108:Ceruletide / Q000494:pharmacology; D002746:Chlorpromazine / Q000494:pharmacology; D002766:Cholecystokinin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D003913:Dextroamphetamine / Q000494:pharmacology; D004558:Electric Stimulation; D005755:Gastrins / Q000493:pharmacokinetics*; D006220:Haloperidol / Q000494:pharmacology; D006728:Hormones / Q000494:pharmacology; D008297:Male; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012653:Self Stimulation; D012844:Sincalide / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013758:Tetragastrin / Q000493:pharmacokinetics*
D014150:Antipsychotic Agents; D005755:Gastrins; D006728:Hormones; D010455:Peptides; D013758:Tetragastrin; D002108:Ceruletide; D002766:Cholecystokinin; D006220:Haloperidol; D012844:Sincalide; D001058:Apomorphine; D003913:Dextroamphetamine; D002746:Chlorpromazine