Characterization of the mu and delta opioid receptors in the brain of the C57BL/6 and DBA/2 mice, selected for their differences in voluntary ethanol consumption

Genetically determined differences in the activity of the hypothalamic beta-endorphin system have been demonstrated between the C57BL/6 (alcohol-preferring) and DBA/2 (alcohol-aversive) inbred strains of mice. The present studies examined the distribution and density of the mu and delta receptors in specific brain regions that may mediate the rewarding and reinforcing effects of ethanol, using quantitative autoradiography and the specific mu antagonist FK 33-824 and delta agonist DPDPE, in their iodinated form. (125)1-FK 33-824 recognizes a high affinity binding site in brain membrane preparations from both the C57BL/6 (K-d = 1.37 +/- 0.22 nM; B-max = 80 +/- 12.3 fmol/mg protein) and DBA/2 mice (K-d = 1.02 +/- 0.16 nM; B-max = 39.5 +/- 9.6 fmol/mg protein), whereas I-125-DPDDPE binds to a high affinity binding site in brain membranes from both the C57BL/6 (K-d = 1.08 +/- 0.34 nM; B-max = 24.4 +/- 4.5 fmol/mg protein) and DBA/2 mice (K-d = 0.68 +/- 0.24 nM; B-max = 15.3 +/- 3.7 fmol/mg protein). The autoradiographic studies demonstrated differences in the density of the mu opioid receptors between the two strains of mice in brain nuclei that are not directly related to the brain reward system. However, strain-related differences in the density of delta opioid receptors were observed in regions of the limbic system known ao mediate the positive reinforcing effect of many drugs of abuse. The density of delta receptors was significantly higher in the ventral tegmental area and nucleus accumbens of the C57BL/6 mice. The results of the present study support the hypothesis that genetically determined differences exist in the density of opioid receptors in distinct regions of the brain between the C57BL/6 and DBA/2 inbred strains of mice, which may play a role in controlling their voluntary ethanol consumption.