title: Exogeneous and endogenous CCK inhibit ethanol ingestion in Sardinian alcohol-preferring rats.
abstract: Ethanol ingestion, like food ingestion, stimulates release of the signaling molecule cholecystokinin (CCK) from the small intestine. Here, we investigated the possibility that ethanol-induced CCK release might be a negative-feedback control of ethanol ingestion, similar to its function as part of the mechanism by which ingested food produces meal-ending satiation. We used Sardinian alcohol-preferring (sP) and Marchesian Sardinian (msP) alcohol-preferring rats, two apparently identical substrains that spontaneously ingest pharmacologically relevant amounts of ethanol, as well as their background strain, Wistar (W) rats. We demonstrated that: (1) intraperitoneal (IP), but not intracerebroventricular, injections of 0.5-4 microg/kg CCK-8 produced transient, dose-related reductions in 10% ethanol ingestion; (2) this inhibitory effect of CCK-8 on ethanol intake appeared behaviorally similar to its inhibitory action on ingestion of sucrose solutions; (3) the inhibitory effect of IP CCK-8 on ethanol ingestion occurred without evidence of tolerance when tests were repeated on consecutive days; (4) IP CCK-8 reduced ethanol intake despite simultaneously reducing blood ethanol levels (BALs); and (5) antagonism of CCK1 receptors with devazepide increased ethanol intake, indicating that endogenous CCK normally limits the size of bouts of ethanol ingestion. These results implicate peripheral CCK in the control of ethanol ingestion in sP and msP alcohol-preferring rats.
authors.affiliation: Department of Psychiatry, E.W. Bourne Behavioral Research Laboratory, New York Presbyterian Hospital, Weill Medical College of Cornell University, White Plains 10605, USA. nori.geary@inw.agrl.ethz.ch
authors.forename: Nori
authors.initials: N
authors.lastname: Geary
authors.forename: Amy
authors.initials: A
authors.lastname: Wolfe
authors.forename: Carlo
authors.initials: C
authors.lastname: Polidori
authors.forename: Federica
authors.initials: F
authors.lastname: Policani
authors.forename: Maurizio
authors.initials: M
authors.lastname: Massi
mesh_terms: D000428:Alcohol Drinking / Q000517:prevention & control*; D000818:Animals; D002766:Cholecystokinin / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology*; D020109:Devazepide / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004327:Drinking Behavior / Q000187:drug effects*; D000431:Ethanol / Q000008:administration & dosage*; D007274:Injections, Intraperitoneal; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D010446:Peptide Fragments; C410885:cholecystokinin 8; D000431:Ethanol; D002766:Cholecystokinin; D020109:Devazepide