| Rapid development of tolerance to the behavioural actions of cholecystokinin. | |
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MedLine Citation:
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PMID: 6300693 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cholecystokinin (CCK) acts acutely to inhibit food consumption in fasted rats, mice, sheep, pigs, monkeys and humans. CCK has been proposed as a satiety signal, inducing the behavioural sequence of satiety, or as an aversive internal stimulus, which inhibits food intake by inducing malaise. Reductions in food intake and related exploratory behaviours are initiated by CCK at its peripheral receptor in the gut, which appears to transmit sensory feedback via the vagus nerve to brain regions mediating appetitive behaviours. The therapeutic potential of CCK as an appetite suppressant in obesity syndromes rests on the demonstration of significant, long-lasting body weight reduction. Chronic CCK administration by repeated injections is problematic, since this peptide is rapidly degraded in vivo. We chose the Alzet constant infusion osmotic minipump to investigate possible alterations in body weight and food intake during continuous infusion of CCK. We now report that no change was detected in either body weight or total daily food consumption at any time point during 2 weeks of intraperitoneally (i.p.) infused CCK. The mechanism underlying the lack of chronic CCK effects appears to be a rapid development of behavioural tolerance. Acute challenge doses of CCK which induced satiety-related behaviours in saline-infused rats were ineffective in CCK-infused rats. The behavioural tolerance was apparent within a few hours of minipump implantation. These results provide the first evidence that rapid and reversible tolerance develops to the actions of a gut peptide. |
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Authors:
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J N Crawley; M C Beinfeld |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Nature Volume: 302 ISSN: 0028-0836 ISO Abbreviation: Nature Publication Date: 1983 Apr |
Date Detail:
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Created Date: 1983-05-27 Completed Date: 1983-05-27 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0410462 Medline TA: Nature Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 703-6 Citation Subset: IM |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Appetite Depressants / pharmacology* Body Weight / drug effects* Cholecystokinin / pharmacology* Drug Tolerance Feeding Behavior / drug effects* Male Peptide Fragments / pharmacology* Rats Rats, Inbred Strains Sincalide |
| Grant Support | |
ID/Acronym/Agency:
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NS 18335/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Appetite Depressants; 0/Peptide Fragments; 25126-32-3/Sincalide; 9011-97-6/Cholecystokinin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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