Effect of ethanol self-administration on μ- and δ-opioid receptor-mediated G-protein activity

Background: This study examined the effects of ethanol self-administration on mu- and delta-opioid receptor-mediated G-protein activity in specific brain regions of male Long Evans rats. Methods: Rats were trained to self-administer ethanol by using a home-cage modification of the sucrose substitution paradigm. After 30 to 40 days of sucrose or sucrose/15% ethanol self-administration (20 min sessions, Monday-Friday), rats were killed for autoradiographic assays. Coronal sections of brains from sucrose and ethanol self-administering rats were collected and processed for basal and mu- and delta-stimulated [S-35]guanosine-5'-O-(y-thio)-triphosphate (GTPgammaS) binding. Sections were exposed to film and then analyzed by using computer-assisted densitometry to determine levels of basal and agonist-stimulated [S-35]GTPgammaS binding. Results: mu-Opioid-stimulated [S-35]GTPgammaS binding was decreased in the prefrontal cortex of brains from ethanol compared with sucrose self-administering rats. mu-Opioid-stimulated [S-35]GTPgammaS binding was unchanged in the cingulate cortex, caudate-putamen, nucleus accumbens, amygdala, hypothalamus, thalamus, and locus ceruleus of ethanol compared with sucrose self-administering rats. Basal and delta-opioid-stimulated [S-35]GTPgammaS binding did not differ between the two groups in the prefrontal cortex or any other region analvzed. Conclusions: These data demonstrate decreased mu-opioid-mediated G-protein activity in the prefrontal cortex of ethanol self-administering rats and suggest an interaction between ethanol and mu-opioid receptors in this region.