DOI: 10.1007/s12640-016-9688-3 Pages: 309-316

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

1. Medical University of Lublin, Chair and Department of Pharmacology and Pharmacodynamics

Correspondence to:
Sylwia Talarek
Tel: +48 81 4487253



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.

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  • Accepted: Dec 1, 2016
  • Online: Dec 12, 2016
  • Revised: Nov 23, 2016

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