| 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. | |
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MedLine Citation:
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PMID: 10734165 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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F Chen; A J Lawrence |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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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:
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Created Date: 2000-04-21 Completed Date: 2000-04-21 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0376362 Medline TA: J Pharmacol Exp Ther Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 159-65 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, Monash University, Clayton, Victoria, Australia. Ffeng.Chen@med.monash.edu.au |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Alcohol Drinking
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metabolism Animals Autoradiography 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* Male Protein Binding / drug effects Rats Rats, Inbred Strains Receptors, Opioid, mu / drug effects* Receptors, Serotonin / drug effects* Receptors, Serotonin, 5-HT1 Substance Withdrawal Syndrome / psychology* |
| Chemical | |
Reg. No./Substance:
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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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