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.
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.
Chen
F
F
Department of Pharmacology, Monash University, Clayton, Victoria, Australia. Ffeng.Chen@med.monash.edu.au
Lawrence
A J
AJ
D000428:Alcohol Drinking / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D001923:Brain Chemistry / Q000187:drug effects*; D002492:Central Nervous System Depressants / Q000009:adverse effects* / Q000494:pharmacology*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D000431:Ethanol / Q000009:adverse effects* / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology*; D008297:Male; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D017450:Receptors, Opioid, mu / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects*; D044263:Receptors, Serotonin, 5-HT1; D013375:Substance Withdrawal Syndrome / Q000523:psychology*
D002492:Central Nervous System Depressants; D017450:Receptors, Opioid, mu; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D000431:Ethanol; D019204:GTP-Binding Proteins