Abstract

Previous studies have shown that chronic ethanol influences the density of central μ-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 [³⁵S]guanosine-5′-O-(3-thio)-triphosphate ([³⁵S]GTPγS) binding stimulated by [d-Ala²,N-MePhe⁴,Gly-ol⁵]-enkephalin (DAMGO) or L694,247 was used. By quantitative autoradiography, receptor-mediated [³⁵S]GTPγS 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 (μ-opioid receptor agonist)-stimulated binding of [³⁵S]GTPγS was obtained in the striatum, nucleus accumbens, and lateral septum, whereas L694,247 (5-hydroxytryptamine_1A/1B/1D receptor agonist)-stimulated binding of [³⁵S]GTPγS was observed in the lateral septum, amygdala, and cingulate cortex. Chronic ethanol self-administration significantly reduced DAMGO-stimulated [³⁵S]GTPγS 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 [³⁵S]GTPγS binding in all tested brain regions. The region-specific and receptor-specific alteration of agonist-stimulated [³⁵S]GTPγS binding suggests that the change of functional coupling of μ-opioid receptors to G proteins induced by chronic ethanol drinking may have a pathophysiological role in the consequences of ethanol consumption.