IMMUNOSUPPRESSION BY MORPHINE IS MEDIATED BY CENTRAL PATHWAYS

We reported previously that a single systemic injection of morphine (1 0 mg/kg) to rats profoundly suppressed mitogen-induced proliferation o f blood lymphocytes by a receptor-mediated mechanism. The present stud y examined whether this immunosuppressive effect of morphine is mediat ed by opioid receptors located at either peripheral or central sites. First, the effects of systemic morphine administration on analgesia, m itogen-stimulated lymphocyte proliferation and corticosterone secretio n were compared to those observed after the systemic administration of N-methylmorphine, a quaternary derivative which does not readily pene trate the blood-brain barrier. In contrast to systemically administere d morphine, the i.p. injection of N-methylmorphine (20 mg/kg) was with out any effect on lymphocyte proliferation, plasma corticosterone conc entrations or analgesic responses. Secondly, the effects of morphine a nd N-methylmorphine after central administration were compared. Within 2 hr after the microinjection of either morphine (1 0 mug/2 mul) or N -methylmorphine (15 mug/2 mul) into the third ventricle, blood lymphoc yte responses were inhibited by 70%, plasma corticosterone concentrati ons were significantly elevated and maximal analgesic responses were p resent. Finally, microinjection of morphine (1 mug/0.2 mul) into the a nterior hypothalamus inhibited blood lymphocyte proliferation by 50% w ithout producing analgesia or a significant increase in plasma cortico sterone. These findings suggest that central opioid pathways are invol ved in the immunosuppressive effects of morphine and these pathways ma y be distinct from those participating in opioid-induced analgesia and adrenal activation.