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From the * Department of Medical and Molecular Genetics, The µ 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 range of diverse biological processes. Using a mouse model in which the receptor
gene was disrupted by targeted homologous recombination, we explored the involvement of
this receptor in a number of physiological functions. Mice homozygous for the disrupted gene
developed normally, but their motor function was altered. Drug-naive homozygotes displayed
reduced locomotor activity, and morphine did not induce changes in locomotor activity observed in wild-type mice. Unexpectedly, lack of a functional receptor resulted in changes in
both the host defense system and the reproductive system. We observed increased proliferation
of granulocyte-macrophage, erythroid, and multipotential progenitor cells in both bone marrow and spleen, indicating a link between hematopoiesis and the opioid system, both of which
are stress-responsive systems. Unexpected changes in sexual function in male homozygotes were also observed, as shown by reduced mating activity, a decrease in sperm count and motility, and smaller litter size. Taken together, these results suggest a novel role of the µ opioid receptor in hematopoiesis and reproductive physiology, in addition to its known involvement in
pain relief.
Department of Microbiology and
Immunology, § Department of Physiology and Biophysics, Department of Medicine, and ¶ Walther
Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202; and the ** Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of
Medicine, Cincinnati, Ohio 45267
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