Journal Article

Up-regulation of neuronal NO synthase immunoreactivity in opiate dependence and withdrawal

Leza, J. C., Rodrigo, J., Bentura, M. L., Moro, M. A., Lorenzo, P., Cuéllar, B., Fernández, A. P., Lizasoain, I.

2000

Overview

Nitric oxide (NO) has been postulated to contribute significantly to analgesic effects of opiates as well as to the development of tolerance and physical dependence to morphine. The present study was undertaken to determine the effect of chronic morphine treatment and abstinence on the expression of neuronal NO synthase (neuronal NOS, nNOS) in several brain regions of mice. Seven days after the implantation of a 75 mg morphine pellet, adult male CD1 mice received a SC dose of 1 mg/kg naloxone. Fifteen minutes after the naloxone injection, brains were removed and nNOS expression was studied by using immunohistochemical methods. Morphine-dependence produced an increase in the number of nNOS-positive cells in the main and accessory olfactory bulb, olfactory nuclei, cerebellum, locus coeruleus, medulla oblongata (nucleus of the solitary tract and prepositus hypoglossal nucleus), and a decrease in nNOS immunoreactivity in hypothalamus. The administration of naloxone to morphine-dependent mice to induce abstinence increased nNOS immunoreactivity in the hypothalamus and locus coeruleus. These results indicate that the chronic treatment with morphine leads to alterations in nNOS expression in important regions implicated in the physical tolerance and dependence to opiates and suggest the use of specific inhibitors of this isoform in these conditions.

• Publisher: Springer,Springer Nature B.V
• Subject: Abstinence / Accessory olfactory bulb / Analgesics / Animals / Biological and medical sciences / Brain - drug effects / Brain - enzymology / Cerebellum / Cerebellum - drug effects / Cerebellum - enzymology / Drug dependence / Drug tolerance / Drug toxicity and drugs side effects treatment / Hypothalamus / Immunohistochemistry / Immunoreactivity / Locus coeruleus / Male / Medical sciences / Medulla oblongata / Medulla Oblongata - drug effects / Medulla Oblongata - enzymology / Mice / Morphine / Morphine - adverse effects / Morphine - pharmacology / Morphine Dependence - enzymology / Morphine Dependence - etiology / Naloxone / Narcotics / Narcotics - adverse effects / Narcotics - pharmacology / Nitric oxide / Nitric Oxide Synthase - analysis / Nitric Oxide Synthase - biosynthesis / Nitric Oxide Synthase Type I / Nitric-oxide synthase / Olfactory bulb / Olfactory Bulb - drug effects / Olfactory Bulb - enzymology / Opioids / Pharmacology. Drug treatments / Solitary tract nucleus / Substance Withdrawal Syndrome - enzymology / Substance Withdrawal Syndrome - etiology / Toxicity: nervous system and muscle / Up-Regulation - drug effects