Document Detail


Effects of intraperitoneal administration of the GABAB receptor positive allosteric modulator 2,6-di tert-butyl-4-(2-hydroxy-2,2-dimethyl-propyl)-phenol (CGP7930) on food intake in non-deprived rats.
MedLine Citation:
PMID:  22652431     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
γ-Aminobutyric acid-(B) (GABA(B)) receptor positive allosteric modulators (PAMs) act on an allosteric site on the GABA(B) receptor to potentiate the effects of GABA and GABA(B) receptor agonists. It has previously been demonstrated that the GABA(B) receptor agonist baclofen increases food intake in non-deprived rats. The aim of this study was to investigate whether the GABA(B) receptor PAM 2,6-di tert-butyl-4-(2-hydroxy-2,2-dimethyl-propyl)-phenol (CGP7930) would (i) increase food intake, and (ii) potentiate the hyperphagic effects of baclofen in rats. In Experiment 1, the effects of intraperitoneal (i.p.) administration of CGP7930 (1, 6 and 12 mg/kg) was investigated on food intake in non-deprived male Wistar rats. The 12 mg/kg dose of CGP7930 significantly increased cumulative food intake 30, 60 and 120 min (P<0.05, in each case) after administration. The 1 and 6 mg/kg doses were without effect. In Experiment 2, the effects of pretreatment with CGP7930 (6 mg/kg; i.p.) 5 min prior to administration of baclofen (2mg/kg, i.p.) was investigated on 30min cumulative food intake in non-deprived male Wistar rats. Baclofen (2mg/kg) significantly increased food intake compared with vehicle treatment (P<0.01). CGP7930 (6 mg/kg) had no effect on feeding. However, pretreatment with CGP7930 (6 mg/kg) significantly potentiated the hyperphagic effects of baclofen (2mg/kg) (P<0.01). These findings show that CGP7930 increases food intake and enhances the hyperphagic effects of baclofen, and are consistent with in vitro studies that suggest that it potentiates the effects of endogenous GABA and GABA(B) receptor agonists by allosteric modulation of the GABA(B) receptor.
Authors:
Ivor S Ebenezer
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-05-28
Journal Detail:
Title:  European journal of pharmacology     Volume:  690     ISSN:  1879-0712     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-07-31     Completed Date:  2012-12-17     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  115-8     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier B.V. All rights reserved.
Affiliation:
Neuropharmacology Research Group, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth PO 1 2DT, United Kingdom. ivor.ebenezer@port.ac.uk
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MeSH Terms
Descriptor/Qualifier:
Allosteric Regulation / drug effects
Animals
Baclofen / pharmacology
Dose-Response Relationship, Drug
Drug Interactions
Eating / drug effects*
GABA-B Receptor Agonists / pharmacology
Hyperphagia / chemically induced,  drug therapy,  metabolism,  physiopathology
Injections, Intraperitoneal
Male
Phenols / administration & dosage*,  pharmacology*,  therapeutic use
Rats
Rats, Wistar
Receptors, GABA-B / metabolism*
Chemical
Reg. No./Substance:
0/2,6-di-tert-butyl-4-(3-hydroxy-2,2-dimethylpropyl)phenol; 0/GABA-B Receptor Agonists; 0/Phenols; 0/Receptors, GABA-B; 1134-47-0/Baclofen

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