Divergent effects of l-arginine-NO pathway modulators on diazepam and flunitrazepam responses in NOR task performance

Orzelska, Jolanta; Talarek, Sylwia; Listos, Joanna; Fidecka, Sylwia

doi:10.1016/j.bbr.2015.02.014

Cited by 9 publications

(12 citation statements)

References 55 publications

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“…Other classic BZ—clonazepam and chlordiazepoxide—also provoked sleep after acute administration in mice (Talarek and Fidecka 2004). Moreover, behavioural studies of Orzelska et al (2013, 2015) with a comparison of DZ and FNZ indicated that NOS inhibitors differentially affected DZ and FNZ responses of rats in the novel object recognition test. These results seem to be pertinent because it can be supposed that different BZ compounds will differ in terms of their side effects and in terms of interactions with drugs that modify the level of NO.…”

Section: Discussionmentioning

confidence: 96%

“…in the ability to induce severe aggressive and disinhibited behaviours (Daderman et al 2002). Our previous behavioural investigations on interactions of NO and BZ showed no differences between diazepam (DZ) and chlordiazepoxide or clonazepam (Talarek and Fidecka 2003; Talarek and Fidecka 2004) but supported atypical properties of FNZ, especially in its influence on cognition (Orzelska et al 2013; Orzelska et al 2015; Orzelska-Gorka et al 2016) and locomotor activity in rodents (Talarek et al 2013). Considering these intriguing data, the choice of FNZ in our present studies seems to be justified.…”

Section: Introductionmentioning

confidence: 92%

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

et al. 2016

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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: N G-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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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 92%

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

et al. 2016

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“…Since brain GABA-T is the subject of this study, the effects of NO on the nervous system, which may have repercussions on GABA-T activity, are of particular interest. For example, it has been reported that NO evokes the release of several neurotransmitters, including GABA (7,24).…”

Section: Resultsmentioning

confidence: 99%

Role of nitric oxide synthase on brain GABA transaminase activity and GABA levels

2018

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In an attempt to clarify the controversial role of nitric oxide (NO) in seizures, the effects of NO on brain GABA transaminase (GABA-T) activity and GABA levels were investigated. To this aim, the effects of the substrate (l-arginine) and inhibitors (Nω-nitro-l-arginine methyl ester, 7-nitroindazole) of NO synthase (NOS) on GABA-T activity and GABA levels in vitro and ex vivo were analyzed. In vitro NO diminished GABA-T activity and increased GABA. Ex vivo NO modified GABA-T activity and GABA levels biphasically. Inhibition of endothelial and neuronal NOS (eNOS and nNOS) had opposite effects on GABA-T activity and GABA levels, even during seizures induced by pentylenetetrazole. Different effects of NO on GABA-T activity and on GABA levels, depending on the NOS isoform involved, may explain its contradictory role in seizures, the endothelial NOS acting as an anticonvulsant and the neuronal NOS as a proconvulsant. nNOS inhibitors may represent a new generation of antiepileptics.

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“…An object recognition test was performed as described elsewhere (Ennaceur and Delacour 1988;Orzelska et al 2015). An apparatus included a square open box, made of plexiglass (63 cm long × 44.5 cm high × 44 cm wide) and illuminated by a lamp (light intensity, 10 lx), suspended 50 cm above the box.…”

Section: Novel Object Recognition Test (Nor)mentioning

confidence: 99%

“…Diazepam (DZ) and flunitrazepam (FNZ) impaired acquisition in the mEPM and the NOR tests. Interestingly, these studies revealed differences in the action of NOS inhibitors on memory impairment induced by DZ or FNZ (Orzelska et al 2013(Orzelska et al , 2015Orzelska-Gorka et al 2016). The main aim of this research was to determine whether sildenafil, an inhibitor of PDE5, and methylene blue (MB), an inhibitor of NO-sensitive sGC, affect amnesic effects caused by DZ and FNZ in the mEPM and NOR tests in mice.…”

Section: Introductionmentioning

confidence: 99%

Modification of NO-cGMP Pathway Differentially Affects Diazepam- and Flunitrazepam-Induced Spatial and Recognition Memory Impairments in Rodents

et al. 2019

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This study investigated the influence of sildenafil and methylene blue (MB), two modulators of the nitric oxide (NO)-cyclic guanosine-3′,5′-monophosphate (cGMP) pathway on amnesic effects of two benzodiazepines (BZs) (diazepam (DZ) and flunitrazepam (FNZ)), in rodents-mice and rats. In the modified elevated plus maze (mEPM) and novel object recognition (NOR) tests, MB given ip at a dose of 5 mg/kg 5 min prior to DZ administration (0.25 or 1 mg/kg, sc) enhanced/induced memory impairment caused by DZ. When MB (2.5, 5, and 10 mg/kg) was applied 5 min prior to FNZ administration (0.05 and 0.1 mg/kg), an effect was opposite and memory impairment induced by FNZ was reduced. When sildenafil (2.5 and 5 mg/kg, ip) was applied 5 min prior to DZ, we observed a reduction of DZ-induced memory deficiency in the mEPM test. A similar effect of sildenafil was shown in the NOR test when the drug was applied at doses of 1.25, 2.5, and 5 mg/kg prior to DZ. In the mEPM test, sildenafil at abovementioned doses had no effects on FNZ-induced memory impairment. In turns, sildenafil administered at doses of 2.5 and 5 mg/kg increased the effect of FNZ on memory impairment in the NOR test. In conclusion, the NO-cGMP pathway is involved differentially into BZs-induced spatial and recognition memory impairments assessed using the NOR and mEPM tests. Modulators of the NO-cGMP pathway affect animal behavior in these tests in a different way depending on what benzodiazepine is applied.

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Divergent effects of l-arginine-NO pathway modulators on diazepam and flunitrazepam responses in NOR task performance

Cited by 9 publications

References 55 publications

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

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

Role of nitric oxide synthase on brain GABA transaminase activity and GABA levels

Modification of NO-cGMP Pathway Differentially Affects Diazepam- and Flunitrazepam-Induced Spatial and Recognition Memory Impairments in Rodents

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