Histo- and immunocytochemical detection of inducible NOS and TNF-α in the locus coeruleus of human opiate addicts

• Published in: Journal of chemical neuroanatomy Vol. 37; no. 2; pp. 65 - 70
• Main Authors: Dyuizen, I., Lamash, N.E.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2009
• Subjects: Adolescent; Adult; Analgesics, Opioid - pharmacology; Biomarkers - analysis; Biomarkers - metabolism; Endothelial Cells - metabolism; Female; Histocytochemistry; Human; Humans; Immunohistochemistry; Locus coeruleus; Locus Coeruleus - metabolism; Locus Coeruleus - physiopathology; Male; NADPH Dehydrogenase - analysis; NADPH Dehydrogenase - metabolism; Neuroglia - metabolism; Neurons - metabolism; Nitric Oxide - metabolism; Nitric oxide synthase; Nitric Oxide Synthase Type II - analysis; Nitric Oxide Synthase Type II - metabolism; Opiates; Opioid-Related Disorders - metabolism; Opioid-Related Disorders - physiopathology; Tumor necrosis factor α; Tumor Necrosis Factor-alpha - analysis; Tumor Necrosis Factor-alpha - metabolism; Up-Regulation - drug effects; Up-Regulation - physiology; Young Adult; Human; Opiates; Nitric oxide synthase; Locus coeruleus; Tumor necrosis factor α
• ISSN: 0891-0618; 1873-6300; 1873-6300
• DOI: 10.1016/j.jchemneu.2008.10.005

In order to determine the role of inducible nitric oxide synthase (iNOS) and tumor necrosis factor-α (TNF-α) in the pathogenesis of opiate addiction in humans, the expression of both was analyzed in the locus coeruleus (LC) of patients who died from heroin overdose. In control subjects, NADPH-diaphorase (NADPHd) histochemistry was mainly observed in non-noradrenerdic neurons, some glial and endothelial cells. However, in the brain of opiate addicts, NADPHd and iNOS expression was detected in noradrenergic LC cells, correlating with an increase in iNOS and TNF-α expression in glial cells as revealed by immunohistochemical and Western blot analyses. These findings indicate that sustained overproduction of cytokine and NO via iNOS expression may be responsible, at least in part, for some neurochemical changes in the locus coeruleus caused by chronic opiate usage in humans.