• R D Mellon and B M Bayer.
• Department of Pharmacology, Georgetown University Medical Center, Washington, DC 20007, USA.
• J. Pharmacol. Exp. Ther. 1999 Feb 1;288(2):635-42.

AbstractAcute administration of morphine alters various neuroendocrine and immune parameters via opioid receptors located within the central nervous system. Similar effects have been reported after systemic nicotine treatment. To examine the possible relationship between opioid and nicotinic receptor activation on the immune system, we compared the effects of morphine with both nicotine and the highly selective nicotinic agonist, epibatidine. Male Sprague-Dawley rats were treated with either morphine (10 mg/kg, s.c.), nicotine (2.85 mg/kg, s.c. = 1 mg/kg freebase), or epibatidine (5 microg/kg, s.c.) and sacrificed 2 hours later. Each drug increased plasma corticosterone levels and decreased the magnitude of the peripheral blood lymphocyte proliferation response to the T cell mitogen concanavalin A. None of the treatments had a significant effect on splenic or thymic lymphocyte responses. The effects of nicotine treatment were dose-dependent. Pretreatment with the quaternary ganglionic antagonist chlorisondamine (0.5 mg/kg, i.p.), completely blocked the effect of epibatidine on blood lymphocytes without altering the elevation of corticosterone levels. Although naltrexone (10 mg/kg, s.c.) blocked all effects of morphine, the effects of epibatidine were not blocked by the opioid receptor antagonist. Furthermore, in contrast to morphine (), central injection of neither nicotine (30 or 240 nmol) nor epibatidine (5, 50, or 500 ng) altered blood lymphocyte responses. These results suggest that, like morphine, nicotinic agonists decrease blood lymphocyte proliferation responses, apparently independent of elevated corticosterone. However, unlike morphine, nicotinic agonists appear to act predominantly at peripheral receptors, suggesting that nicotinic receptors are downstream of opioid receptors in a centrally mediated opioid-induced immunomodulatory pathway.

44 keywords...

hide…