Differential effects of buprenorphine and morphine on immune and neuroendocrine functions following acute administration in the rat mesencephalon periaqueductal gray.
The effects of the mu-opioid receptor agonists buprenorphine and morphine on immune and neuroendocrine functions through acute action in the rat mesencephalon periaqueductal gray (PAG) were evaluated. Buprenorphine is an analgesic recently approved for the treatment of drug dependency. In this study, it was shown that injection of an equianalgesic dose of buprenorphine (related to morphine) into the ventral-caudal PAG did not alter splenic NK cell, T cell, and macrophage functions, whereas morphine significantly (p<0.001) suppressed splenic NK cell cytotoxic activity (14-50% reduction), splenic and thymic T cell proliferation to concanavalin A (Con A, 43-76% reduction), antiTCR (T cell receptor) (85% reduction) and IL-2 (36-48% reduction), and macrophage functions including nitric oxide (36-41% reduction) and TNF-alpha production (26%), and phagocytosis of Candida albicans (39%). In addition, buprenorphine was associated with significant (p<0.0001) reductions in adrenocorticotropic hormone (ACTH) and corticosterone (CSO) plasma levels, without altering norepinephrine (NE) and serotonin splenic dialysate levels. In contrast, morphine significantly (p<0.0001) increased glucocorticoid and catecholamine levels in plasma and spleen dialysates, respectively. These results indicated that buprenorphine did not activate either the hypothalamic-pituitary-adrenal (HPA) axis with glucocorticoid release, or the sympathetic nerve (SNS) activity with bioamine production, and was not associated with immunosuppression. The lack of effects of buprenorphine on neuroendocrine systems may be related to its partial agonist properties, the absence of effects on immune system function, and may be associated with the reduction in craving observed in addictive disorders.
Section of Medical Sciences, Department of Biomedical and Therapeutic Sciences, University of Illinois College of Medicine at Peoria, 61656-1649, USA.
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Gomez-Flores
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Weber
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D002047:Buprenorphine / Q000008:administration & dosage*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D007111:Immunity, Cellular / Q000187:drug effects*; D007276:Injections, Intraventricular; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D008636:Mesencephalon / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D009020:Morphine / Q000008:administration & dosage*; D009490:Neurosecretory Systems / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism; D010487:Periaqueductal Gray / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344
D002047:Buprenorphine; D009020:Morphine; D000324:Adrenocorticotropic Hormone; D009638:Norepinephrine