Chronic Ethanol Consumption Reduces 8δ-and μ-Opioid Receptor-Stimulated G-Protein Coupling in Rat Brain

L. C. Saland, A. Abeyta, S. Frausto, M. Raymond-Stintz, C. M. Hastings, M. Carta, C. F. Valenzuela, D. D. Savage
Alcoholism: Clinical & Experimental Research. 2004-01-01; 28(1): 98-104
DOI: 10.1097/01.ALC.0000108658.00243.BF

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1. Alcohol Clin Exp Res. 2004 Jan;28(1):98-104.

Chronic ethanol consumption reduces delta-and mu-opioid receptor-stimulated
G-protein coupling in rat brain.

Saland LC(1), Abeyta A, Frausto S, Raymond-Stintz M, Hastings CM, Carta M,
Valenzuela CF, Savage DD.

Author information:
(1)Department of Neurosciences, University of New Mexico School of Medicine,
Albuquerque, New Mexico, USA.

BACKGROUND: Ethanol consumption is thought to enhance the release of endogenous
opioids acting at opioid receptors (ORs) in the central nervous system. Prior
studies have shown that chronic ethanol consumption in alcohol-preferring rats
uncouples mu-ORs from Gi proteins. The purpose of this study was to investigate
the potential for uncoupling of the delta- and the mu-OR after chronic ethanol
consumption in a nonpreferring rat strain.
METHODS: We used radiohistochemical methods to study mu- and delta-OR-stimulated
G-protein coupling in brain tissue of rats ingesting liquid diets containing 6.7%
ethanol (v/v) for 16 days, as compared with 0% ethanol pair-fed control rats.
Sections of brain from pair-fed and ethanol-treated rats were incubated with
guanylyl 5′-[gamma-[35S]-thio]-triphosphate ([35S]-GTPgammaS) in the absence and
presence of d-Pen2,d-Pen5 enkephalin (DPDPE), a delta-OR agonist, or
Tyr-d-Ala-Gly-N(me)Phe-Gly-ol-enkephalin (DAMGO), a mu-OR agonist.
RESULTS: DPDPE significantly stimulated [35S]-GTPgammaS binding in the
hippocampal dentate gyrus (DG), CA1, cerebellum, and inferior colliculus of
untreated pair-fed controls. By contrast, DPDPE-stimulated [35S]-GTPgammaS
binding was reduced significantly in those brain regions in the ethanol-consuming
group. DAMGO stimulated [35S]-GTPgammaS binding in cortex, caudate, nucleus
accumbens, DG, CA1, and superior and inferior colliculi, whereas the DG, CA1, and
colliculi showed a significant reduction of binding after chronic ethanol. Basal
[35S]-GTPgammaS binding was not different between the two diet groups.
CONCLUSIONS These data are the first to demonstrate functional uncoupling of
delta-ORs from G proteins after chronic ethanol consumption. Uncoupling may
result from modulation of receptors, possibly by internalization or
phosphorylation. Alterations in functional coupling of both delta- and mu-ORs and
subsequent effects may contribute to continued ethanol consumption.

DOI: 10.1097/01.ALC.0000108658.00243.BF
PMID: 14745307 [Indexed for MEDLINE]

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