THE EFFECTS OF REPEATED MORPHINE EXPOSURE ON MU-OPIOID RECEPTOR NUMBER AND AFFINITY IN C57BL 6J AND DBA/2J MICE/

C57BL/6J (B6) mice self-administer substantial quantities of morphine compared to DBA/2J (D2) mice, and most of the genetic component of thi s strain difference has been attributed to a locus on chromosome 10 in the vicinity of the mu opioid receptor gene. To compare binding chara cteristics of mu opioid receptor populations between the two strains, mice were given single daily injections of a long-acting preparation o f morphine sulfate (80 mg/kg, sc) or saline for a period of seven days , and euthanatized six hours after the last injection. Brains were rem oved and dissected into specific regions. Receptor binding studies wer e performed on frontal cortex and striatum. Data were analyzed using n on-linear regression, and K-d and B-max comparisons made between strai ns and treatments, Specific [H-3]DAMGO binding in striatum indicates t hat the density of mu opioid receptors in saline-treated B6 mice and s aline-treated D2 mice does not differ significantly. After repeated mo rphine injection, B6 mice exhibited a decrease in striatal [H-3]DAMGO binding, indicating a downregulation of receptor density by approximat ely 45% (p=.0003 vs saline-treated B6), a phenomenon not observed in D 2 mice. In frontal cortex, no differences in [H-3]DAMGO binding were o bserved between strains or treatment groups. These results demonstrate a significant difference between mu opioid receptor regulation in B6 and D2 mice, and may underlie well documented strain differences in sp ecific opioid-related behaviors.