ALTERED HEMATOPOIESIS, BEHAVIOR, AND SEXUAL FUNCTION IN MU-OPIOID RECEPTOR-DEFICIENT MICE

The mu opioid receptor is thought to be the cellular target of opioid narcotics such as morphine and heroin, mediating their effects in both pain relief and euphoria. Its involvement is also implicated in a ran ge of diverse biological processes. Using a mouse model in which the r eceptor gene was disrupted by targeted homologous recombination, we ex plored the involvement of this receptor in a number of physiological f unctions. Mice homozygous for the disrupted gene developed normally, b ut their motor function was altered. Drug-naive homozygotes displayed reduced locomotor activity, and morphine did not induce changes in loc omotor activity observed in wild-type mice. Unexpectedly, lack of a fu nctional receptor resulted in changes in both the host defense system and the reproductive system. We observed increased proliferation of gr anulocyte-macrophage, erythroid, and multipotential progenitor cells i n both bone marrow and spleen, indicating a link between hematopoiesis and the opioid system, both of which are stress-responsive systems. U nexpected changes in sexual function in male homozygotes were also obs erved, as shown by reduced mating activity, a decrease in sperm count and motility, and smaller litter size. Taken together, these results s uggest a novel role of the mu opioid receptor in hematopoiesis and rep roductive physiology, in addition to its known involvement in pain rel ief.