Altered hematopoiesis, behavior, and sexual function in mu opioid receptor-deficient mice
by
Tian M, Broxmeyer HE, Fan Y, Lai Z, Zhang S, Aronica S, Cooper S, Bigsby RM, Steinmetz R, Engle SJ, Mestek A, Pollock JD, Lehman MN, Jansen HT, Ying M, Stambrook PJ, Tischfield JA, Yu L
Department of Medical and Molecular Genetics,
Indiana University School of Medicine,
Indianapolis 46202, USA.
J Exp Med 1997 Apr 21; 185(8):1517-22

ABSTRACT

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 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 mu opioid receptor in hematopoiesis and reproductive physiology, in addition to its known involvement in pain relief.

Mu
Pain
Heroin
SOD mu
Tolerance
Methadone
Receptor subtypes
Morphine/verapamil
Fentanyl and ketamine
Dynorphin and dopamine
Genes, pharmacology and mu
Depression, opioids and the HPA
Kappa upregulation and addiction
Opioids, Depression and Learned Helplessness

HOME
HedWeb
BLTC Research
Designer Drugs
Paradise-Engineering
The Hedonistic Imperative
When Is It Best To Take Crack Cocaine?