Document Detail


Rapid development of tolerance to the behavioural actions of cholecystokinin.
MedLine Citation:
PMID:  6300693     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
J N Crawley; M C Beinfeld
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Nature     Volume:  302     ISSN:  0028-0836     ISO Abbreviation:  Nature     Publication Date:  1983 Apr 
Date Detail:
Created Date:  1983-05-27     Completed Date:  1983-05-27     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0410462     Medline TA:  Nature     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  703-6     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
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:
NS 18335/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Appetite Depressants; 0/Peptide Fragments; 25126-32-3/Sincalide; 9011-97-6/Cholecystokinin

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