Document Detail

Effect of chronic ethanol and withdrawal on the mu-opioid receptor- and 5-Hydroxytryptamine(1A) receptor-stimulated binding of [(35)S]Guanosine-5'-O-(3-thio)triphosphate in the fawn-hooded rat brain: A quantitative autoradiography study.
MedLine Citation:
PMID:  10734165     Owner:  NLM     Status:  MEDLINE    
Previous studies have shown that chronic ethanol influences the density of central mu-opioid receptors and serotonin(1A) (5-hydroxytryptamine(1A)) receptors. To determine whether the functional coupling of these two receptors to G proteins in the rat brain, particularly in mesocorticolimbic regions, is affected by ethanol, receptor-mediated [(35)S]guanosine-5'-O-(3-thio)-triphosphate ([(35)S]GTPgammaS) binding stimulated by [D-Ala(2),N-MePhe(4),Gly-ol(5)]-enkephalin (DAMGO) or L694,247 was used. By quantitative autoradiography, receptor-mediated [(35)S]GTPgammaS binding activated by the two agonists was mapped throughout brain sections at the level of the nucleus accumbens and hippocampus from groups of alcohol-preferring Fawn-Hooded (FH) rats after different ethanol consumption paradigms. Significant DAMGO (mu-opioid receptor agonist)-stimulated binding of [(35)S]GTPgammaS was obtained in the striatum, nucleus accumbens, and lateral septum, whereas L694,247 (5-hydroxytryptamine(1A/1B/1D) receptor agonist)-stimulated binding of [(35)S]GTPgammaS was observed in the lateral septum, amygdala, and cingulate cortex. Chronic ethanol self-administration significantly reduced DAMGO-stimulated [(35)S]GTPgammaS binding in the nucleus accumbens (-19%), lateral septum (-15%), and striatum (-23%), which recovered toward control levels after ethanol withdrawal. However, chronic ethanol, as well as ethanol withdrawal, failed to produce any significant alteration in L694,247-stimulated [(35)S]GTPgammaS binding in all tested brain regions. The region-specific and receptor-specific alteration of agonist-stimulated [(35)S]GTPgammaS binding suggests that the change of functional coupling of mu-opioid receptors to G proteins induced by chronic ethanol drinking may have a pathophysiological role in the consequences of ethanol consumption.
F Chen; A J Lawrence
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  293     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  2000 Apr 
Date Detail:
Created Date:  2000-04-21     Completed Date:  2000-04-21     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  159-65     Citation Subset:  IM    
Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
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MeSH Terms
Alcohol Drinking / metabolism
Brain Chemistry / drug effects*
Central Nervous System Depressants / adverse effects*,  pharmacology*
Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / pharmacology
Ethanol / adverse effects*,  pharmacology*
GTP-Binding Proteins / metabolism
Guanosine 5'-O-(3-Thiotriphosphate) / pharmacology*
Protein Binding / drug effects
Rats, Inbred Strains
Receptors, Opioid, mu / drug effects*
Receptors, Serotonin / drug effects*
Receptors, Serotonin, 5-HT1
Substance Withdrawal Syndrome / psychology*
Reg. No./Substance:
0/Central Nervous System Depressants; 0/Receptors, Opioid, mu; 0/Receptors, Serotonin; 0/Receptors, Serotonin, 5-HT1; 100929-53-1/Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; 37589-80-3/Guanosine 5'-O-(3-Thiotriphosphate); 64-17-5/Ethanol; EC 3.6.1.-/GTP-Binding Proteins

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

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