Document Detail


Satiety enhancement by selective orexin-1 receptor antagonist SB-334867: influence of test context and profile comparison with CCK-8S.
MedLine Citation:
PMID:  15836896     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Acute systemic treatment with the selective orexin-1 (OX1R) antagonist SB-334867 reduces food intake in rats, an effect associated with an acceleration in behavioural satiety and unrelated to gross behavioural disruption, alterations in palatability, or toxicity. However, as enhanced satiety is behaviourally indexed by an earlier-than-normal transition from eating to resting, and since orexin-A has been implicated in mechanisms of arousal, it remains possible that sedation contributes to the anorectic effect of acute OX1R blockade. Previous work has shown that, when treated with SB-334867 (30 mg/kg, i.p.) 30 min before a 1h test with palatable food, rats begin to show appreciable levels of resting 10-15 min earlier than under control conditions (i.e. around 20 min versus 30-35 min into the session). The present results demonstrate that a 20 min increase in the injection-test interval (i.e. 50 min) had no significant impact on the anorectic, behavioural or weight gain effects of SB-334867 in non-deprived male rats. Most importantly, this altered treatment regimen led to a temporal profile of resting virtually identical to that previously observed with the more conventional 30 min injection-test interval. Although parallel studies indicated that the OX1R antagonist accelerated the onset of resting (and suppressed most active behaviours) even in the absence of food, an equianorectic dose of the natural satiety-related signal cholescystokinin octapeptide (CCK-8S; 5 microg/kg, i.p.) also produced very similar behavioural effects regardless of the presence of food. Together with evidence that SB-334867 preserves the structural integrity of natural feeding behaviour, does not induce nausea/illness or alter taste/palatability and fails to influence EEG measures of arousal/sleep, the present findings are consistent with the view that acute OX1R antagonism selectively enhances satiety. However, unlike the immediate short-circuiting of the satiety sequence induced by CCK-8S, the slower response to SB-334867 implies a more indirect mechanism of action.
Authors:
Y Ishii; J E Blundell; J C G Halford; N Upton; R Porter; A Johns; R J Rodgers
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-12-18
Journal Detail:
Title:  Behavioural brain research     Volume:  160     ISSN:  0166-4328     ISO Abbreviation:  Behav. Brain Res.     Publication Date:  2005 May 
Date Detail:
Created Date:  2005-04-19     Completed Date:  2005-07-05     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8004872     Medline TA:  Behav Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  11-24     Citation Subset:  IM    
Affiliation:
Behavioural Neuroscience Laboratory, Institute of Psychological Sciences, University of Leeds, LS2 9JT, UK.
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Animals
Appetite / drug effects
Behavior, Animal
Benzoxazoles / pharmacology*
Body Weight / drug effects
Drinking / drug effects
Eating / drug effects
Food Deprivation
Male
Nootropic Agents / pharmacology*
Rats
Reaction Time / drug effects
Receptors, G-Protein-Coupled
Receptors, Neuropeptide / antagonists & inhibitors*
Satiety Response / drug effects*
Sincalide / analogs & derivatives*,  pharmacology*
Time Factors
Urea / analogs & derivatives*,  pharmacology*
Chemical
Reg. No./Substance:
0/1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; 0/8-sulfocholecystokinin octapeptide; 0/Benzoxazoles; 0/Nootropic Agents; 0/Receptors, G-Protein-Coupled; 0/Receptors, Neuropeptide; 0/orexin receptors; 25126-32-3/Sincalide; 57-13-6/Urea

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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