Nitroxidergic modulation of behavioural, cardiovascular and immune responses, and brain NADPH diaphorase activity upon morphine tolerance/dependence in rats

作者：Tsakova Ana; Surcheva Slavina; Simeonova Katerina; Altankova Iskra; Marinova Tsvetanka; Usunoff Kamen; Vlaskovska Mila^*

来源：Biotechnology & Biotechnological Equipment, 2015, 29(1): 92-100.

DOI：10.1080/13102818.2014.990924

• morphine tolerance
• dependence
• L-NAME
• behaviour
• cardiovascular
• thymocyte apoptosis
• lymphocyte proliferation
• NOS

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 (N-G-nitro-L-arginine methyl ester) was applied to reveal the role of NOS/NO pathway in the modulation of morphine-induced in vivo and in vitro responses. 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.

• 出版日期2015-1-2