title: Nitroxidergic modulation of behavioural, cardiovascular and immune responses, and brain NADPH diaphorase activity upon morphine tolerance/dependence in rats.
abstract: Opioid and non-opioid effects of acute and chronic morphine administration on behaviour, cardiovascular responses, cell proliferation and apoptosis and nitric-oxide synthase (NOS) activity were studied in rats. A novel score-point scale was introduced to quantify the signs of opioid withdrawal syndrome. NOS inhibitor L-NAME (NG-nitro-L-arginine methyl ester) was applied to reveal the role of NOS/NO pathway in the modulation of morphine-inducedin vivoandin vitroresponses. The obtained data showed that chronic co-administration of L-NAME drastically attenuated naloxone-precipitated withdrawal syndrome and prevented the development of morphine tolerance to cardiovascular action of morphine. The apoptotic process was very much restricted by L-NAME supplementation of chronic morphine treatment, which resulted in few apoptotic cells, less low molecular weight genomic DNA and preservation of high molecular weight non-fragmented genomic DNA. The study provides new data for nitroxidergic modulation of opioid tolerance and dependence.
authors.affiliation: Department of Pharmacology and Toxicology, Medical Faculty, Medical University of Sofia , Sofia , Bulgaria.
authors.forename: Ana
authors.initials: A
authors.lastname: Tsakova
authors.affiliation: Department of Pharmacology and Toxicology, Medical Faculty, Medical University of Sofia , Sofia , Bulgaria.
authors.forename: Slavina
authors.initials: S
authors.lastname: Surcheva
authors.affiliation: Department of Pharmacology and Toxicology, Medical Faculty, Medical University of Sofia , Sofia , Bulgaria.
authors.forename: Katerina
authors.initials: K
authors.lastname: Simeonova
authors.affiliation: Department of Biology, Medical Genetics and Microbiology, Faculty of Medicine, Sofia University "St. Kliment Ohridski" , Sofia , Bulgaria.
authors.forename: Iskra
authors.initials: I
authors.lastname: Altankova
authors.affiliation: Department of Biology, Medical Genetics and Microbiology, Faculty of Medicine, Sofia University "St. Kliment Ohridski" , Sofia , Bulgaria.
authors.forename: Tsvetanka
authors.initials: T
authors.lastname: Marinova
authors.affiliation: Department of Anatomy, Histology and Embryology, Medical Faculty, Medical University of Sofia , Sofia , Bulgaria.
authors.forename: Kamen
authors.initials: K
authors.lastname: Usunoff
authors.affiliation: Department of Pharmacology and Toxicology, Medical Faculty, Medical University of Sofia , Sofia , Bulgaria.
authors.forename: Mila
authors.initials: M
authors.lastname: Vlaskovska
keywords: L-NAME; NOS; behaviour; cardiovascular; lymphocyte proliferation; morphine tolerance/dependence; thymocyte apoptosis