The Importance of l-Arginine:NO:cGMP Pathway in Tolerance to Flunitrazepam in Mice

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• 作者：Sylwia Talarek ; Joanna Listos ; Jolanta Orzelska-Gorka…
• 关键词：Nitric oxide ; Flunitrazepam ; Motor impairment ; Tolerance ; mice
• 刊名：Neurotoxicity Research
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：31
• 期：2
• 页码：309-316
• 全文大小：425KB
• 刊物主题：Neurosciences; Neurology; Neurochemistry; Pharmacology/Toxicology; Neurobiology; Cell Biology;
• 出版者：Springer US
• ISSN：1476-3524
• 卷排序：31

文摘

The goal of the study was to investigate the effects of drugs modifying l-arginine:NO:cGMP pathway on the development of tolerance to flunitrazepam (FNZ)-induced motor impairment in mice. FNZ-induced motor incoordination was assessed on the 1st and 8th days of experiment, using the rotarod and chimney tests. It was found that (a) both a non-selective nitric oxide synthase (NOS) inhibitor: NG-nitro-l-arginine methyl ester (l-NAME) and an unselective neuronal NOS inhibitor: 7-nitroindazole (7-NI) inhibited the development of tolerance to the motor-impairing effects of FNZ in the rotarod and the chimney tests and (b) both a NO precursor: l-arginine and a selective inhibitor of phosphodiesterase 5 (PDE5): sildenafil did not affect the development of tolerance to FNZ-induced motor impairment in mice. Those findings provided behavioural evidence that NO could contribute an important role in the development of tolerance to FNZ in mice.