Quantitative autoradiography of mu-opioid receptors in the CNS of alcohol-naive alcohol-preferring P and -nonpreferring NP rats.

The densities of mu-opioid binding sites in the CNS of alcohol-naive adult male P and NP rats (N = 9 each line) were examined using quantitative autoradiography. Coronal sections (20 microm) were prepared from frozen brains and incubated in 5 nM [3H]DAMGO to label mu-opioid receptor sites. Nonspecific binding was determined in the presence of 1 microM DAMGO. The amount of [3H]DAMGO binding was (a) 20-25% higher in the olfactory tubercle, nucleus accumbens shell and core, and basolateral and lateral amygdaloid nuclei; (b) 15% higher in the lateral septal intermediate nucleus and caudate-putamen patches; and (c) 10-30% lower in the pyramidal and radiatum layers in the CA1 region of the anterior dorsal hippocampus, ventral dentate gyrus and CA1 pyramidal layer of the posterior hippocampus, and posterior medial cortical amygdaloid nucleus of the P compared to the NP rat. No line differences were found in any of the other regions examined (e.g., the cerebral cortical subregions and layers, thalamic nuclei, ventral tegmental area, ventral pallidum, lateral hypothalamus, other regions of the hippocampus, and several subcortical structures). The innate differences in the amount of binding to mu-opioid recognition sites in certain limbic structures, such as the nucleus accumbens, amygdala, and olfactory tubercle, of the P and NP lines may be factors contributing to their disparate alcohol drinking characteristics.