Quantitative autoradiography of mu-opioid receptors in the CNS of high-alcohol-drinking (HAD) and low-alcohol-drinking (LAD) rats

Background: The binding of [³H]DAMGO to mu‐opioid sites was measured in the CNS of selectively bred high–alcohol‐drinking (HAD) and low–alcohol‐drinking (LAD) rats to test the hypothesis that high alcohol preference is associated with higher densities of mu‐opioid receptors. Methods: Adult, alcohol‐naïve male HAD and LAD rats from replicate line 1 were decapitated and their brains frozen in isopentane. Brain sections were incubated with 5 nM [³H]DAMGO, and nonspecific binding was determined in the presence of unlabeled DAMGO. Films were exposed for 60 days, then analyzed using quantitative autoradiography. Results: The densities of [³H]DAMGO binding sites were measured within subregions of neocortex, limbic system, basal ganglia, diencephalon, and brainstem. LAD rats had significantly higher [³H]DAMGO binding (10–30%) than HAD rats within the anterior dorsal hippocampus (CA2), posterior hippocampus (dorsal CA1, and ventral CA1, CA3, and dentate gyrus), thalamus (medial dorsal, lateral, medial dorsal, central, ventral lateral, ventral medial, and ventral medial geniculate nuclei), habenula, and amygdala. No significant interline differences were found in the prefrontal, cingulate, frontal, parietal, temporal, occipital or entorhinal cortices, olfactory tubercle, nucleus accumbens, lateral septum, ventral tegmental area, hypothalamus, caudate‐putamen, substantia nigra, claustrum, central gray, or superior colliculus. Conclusions: The present findings with the HAD and LAD lines do not support the hypothesis that high alcohol preference is associated with higher densities of CNS mu‐opioid receptors. Instead, the present results, in combination with previously published findings, suggest that the mu‐opioid system may play a complex role in regulating high–alcohol‐drinking behavior.