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

Background: The binding of [H-3]DAMGO to mu-opioid sites was measured in th e CNS of selectively bred high-alcohol-drinking (HAD) and low-alcohol-drink ing (LAD) rats to test the hypothesis that high alcohol preference is assoc iated with higher densities of mu-opioid receptors. Methods: Adult, alcohol-naive male HAD and LAD rats from replicate line 1 w ere decapitated and their brains frozen in isopentane. Brain sections were incubated with 5 nM [H-3]DAMGO, and nonspecific binding was determined in t he presence of unlabeled DAMGO. Films were exposed for 60 days, then analyz ed using quantitative autoradiography. Results: The densities of [H-3]DAMGO binding sites were measured within sub regions of neocortex, limbic system, basal ganglia, diencephalon, and brain stem. LAD rats had significantly higher [H-3]DAMGO binding (10-30%) than HA D rats within the anterior dorsal hippocampus (CA2), posterior hippocampus (dorsal CA1, and ventral CA1, CA3, and dentate gyrus), thalamus (medial dor sal, lateral, medial dorsal, central, ventral lateral, ventral medial, and ventral medial geniculate nuclei), habenula, and amygdala, No significant i nterline differences were found in the prefrontal, cingulate, frontal, pari etal, temporal, occipital or entorhinal cortices, olfactory tubercle, nucle us 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 dens ities of CNS mu-opioid receptors. Instead, the present results, in combinat ion with previously published findings, suggest that the mu-opioid system m ay play a complex role in regulating high-alcohol-drinking behavior.