title: The Importance of L-Arginine:NO:cGMP Pathway in Tolerance to Flunitrazepam in Mice.
abstract: 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.
authors.affiliation: Chair and Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Chodzki 4A, 20-093, Lublin, Poland. sylwia.talarek@umlub.pl.
authors.forename: Sylwia
authors.initials: S
authors.lastname: Talarek
authors.affiliation: Chair and Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Chodzki 4A, 20-093, Lublin, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Listos
authors.affiliation: Chair and Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Chodzki 4A, 20-093, Lublin, Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Orzelska-Gorka
authors.affiliation: Chair and Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Chodzki 4A, 20-093, Lublin, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Jakobczuk
authors.affiliation: Chair and Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Chodzki 4A, 20-093, Lublin, Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Kotlinska
authors.affiliation: Chair and Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Chodzki 4A, 20-093, Lublin, Poland.
authors.forename: Grazyna
authors.initials: G
authors.lastname: Biala
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D006152:Cyclic GMP / Q000502:physiology; D004347:Drug Interactions; D004361:Drug Tolerance / Q000502:physiology*; D005445:Flunitrazepam / Q000494:pharmacology*; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D009048:Motor Skills / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D000068677:Sildenafil Citrate / Q000494:pharmacology
chemical_list: D007191:Indazoles; D009569:Nitric Oxide; D005445:Flunitrazepam; D001120:Arginine; D000068677:Sildenafil Citrate; D006152:Cyclic GMP; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester
keywords: Flunitrazepam; Motor impairment; Nitric oxide; Tolerance, mice