The nitric oxide synthesis inhibitor L-NAME produces anxiogenic-like effects in the rat elevated plus-maze test, but not in the social interaction test

Vale, A. L.; Green, Simon; Montgomery, A. M. J.; Shafi, S.

doi:10.1177/026988119801200306

Cited by 48 publications

(26 citation statements)

References 24 publications

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“…These results conform with studies of Vale et al (1998) after intraperitoneal (i.p.) injection of L-NAME.…”

Section: Discussionsupporting

confidence: 91%

“…There is growing evidence that NO is involved in the regulation of anxiety, although some controversial results have been reported. On the one hand, the NOS inhibitor N g -nitro-L-arginine (L-NOARG) abolished the anxiolytic-like effects of NO (Caton et al, 1994) as well as of chlordiazepoxide (Quock and Nguyen, 1992), and the NOS inhibitor N w -nitro-L-arginine methyl ester (L-NAME) produced anxiogenic-like effects in the rat elevated plusmaze (Vale et al, 1998). On the other hand, an anxiolyticlike action of L-NAME has also been reported in the same model (Volke et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

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Stimulation of P2Y1 Receptors Causes Anxiolytic-like Effects in the Rat Elevated Plus-maze: Implications for the Involvement of P2Y1 Receptor-Mediated Nitric Oxide Production

Kittner

Franke

Fischer

et al. 2002

Neuropsychopharmacol

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(ADPbS), the P2X 1,3 receptor agonist a,b-methylene ATP (a,bmeATP), the unspecific P2 receptor antagonist pyridoxalphosphate-6-azopheny l-2 0 ,4 0 -disulfonic acid (PPADS), and the specific P2Y 1 receptor antagonist N 6 -methyl-2 0 -deoxyadenosine-3 0 ,5 0 -bisphosphate (MRS 2179) on the elevated plus-maze behavior of the rat were investigated. All tested compounds were given intracerebroventricularly (0.5 ml). ADPbS (50 and 500 fmol) produced an anxiolytic-like behavioral profile reflected by an increase of the open arm exploration. The anxiolytic-like effects were antagonized by pretreatment with PPADS (5 pmol) or MRS 2179 (5 pmol). Both compounds caused anxiogenic-like effects when given alone. Furthermore, the anxiolytic-like effects of ADPbS could be antagonized by pretreatment with the nitric oxide synthase (NOS) inhibitor N w -nitro-L-arginine methyl ester (L-NAME). In addition, the anxiogenic-like effects of PPADS were reversed by the pretreatment with L-arginine (500 pmol), which is the natural substrate for NOS, but not by D-arginine (500 pmol), which is not. Immunofluorescence staining revealed the presence of P2Y 1 receptors on neurons in different brain regions such as hypothalamus, amygdala, hippocampus and the periaqueductal gray. Furthermore, the colocalization of P2Y 1 receptors and neuronal NOS (nNOS) on some neurons in these regions could be demonstrated. The highest density of P2Y 1 -and nNOS-immunoreactivity was detected in the dorsomedial hypothalamic nucleus. Taken together, the present results suggest that P2Y 1 receptors are involved in the modulation of anxiety in the rat. The anxiolytic-like effects after stimulation of P2Y 1 receptors seem to be in close connection with the related nitric oxide production.

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“…These results conform with studies of Vale et al (1998) after intraperitoneal (i.p.) injection of L-NAME.…”

Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Stimulation of P2Y1 Receptors Causes Anxiolytic-like Effects in the Rat Elevated Plus-maze: Implications for the Involvement of P2Y1 Receptor-Mediated Nitric Oxide Production

Kittner

Franke

Fischer

et al. 2002

Neuropsychopharmacol

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“…In the present study, the NO donor detanonoate mimicked the anxiolytic effects of diazepam in the three behavioral tests, whereas the NOS inhibitor L-NAME produced behavioral effects similar to those observed after restraint stress. These effects of NO donors and inhibitors are consistent with the results of earlier studies (De Oliveira et al, 1997;Vale et al, 1998;Monzón et al, 2001;Masood et al, 2003).…”

Section: Downloaded Fromsupporting

confidence: 91%

Anxiolytic Effects of Phosphodiesterase-2 Inhibitors Associated with Increased cGMP Signaling

Masood

Huang²,

Hajjhussein³

et al. 2009

J Pharmacol Exp Ther

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“…A number of research groups have indeed reported that suppression of NO production can induce anxiogenic-like behavior in a variety of animal models of experimental anxiety Vale et al, 1998;Monzon et al, 2001;Pokk and Vali, 2002;Czech et al, 2003). That NO is involved in reduction of anxiety is supported by the observation that administration of the NO donor 3-morpholinosyndnonimine (SIN-1) evoked an anxiolytic-like response in mice in the light/dark exploration test (Li and Quock, 2002).…”

Section: Discussionmentioning

confidence: 99%

Antagonism by NOS Inhibition of the Behavioral Effects of Benzodiazepine and GABAA Receptor Agonists in the Mouse Elevated Plus-Maze

Elfline

Branda

Babich

et al. 2004

Neuropsychopharmacol

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Earlier we implicated nitric oxide (NO) in mediation of the behavioral effects of benzodiazepines. Since benzodiazepines work through facilitation of GABAergic inhibitory neurotransmission, this study was designed to determine whether the direct-acting g-aminobutyric acid A (GABA A ) receptor agonist THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) evokes behavioral effects similar to those of benzodiazepines and whether behavioral effects of THIP are also NO dependent. When challenged with either chlordiazepoxide or THIP in an elevated plus-maze paradigm, male NIH Swiss mice exhibited a dose-related increase in open-arm activity. The chlordiazepoxide-induced effects were sensitive to antagonism by a benzodiazepine antagonist, and the effects of THIP were blocked by a GABA A receptor antagonist. Pretreatment with the NO synthase (NOS) inhibitor L-N G -nitro arginine antagonized the effects of both chlordiazepoxide and THIP; similar pretreatment with the D-isomer, D-N G -nitro arginine, which is inactive as an NOS inhibitor, was without effect on chlordiazepoxide and THIP. These findings indicate that chlordiazepoxide and THIP evoke similar behavioral effects in mice in the elevated plus-maze through actions on different parts of the GABA A receptor, and that NO appears to play a key role in mediation of the behavioral effects of both chlordiazepoxide and THIP.

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The nitric oxide synthesis inhibitor L-NAME produces anxiogenic-like effects in the rat elevated plus-maze test, but not in the social interaction test

Cited by 48 publications

References 24 publications

Stimulation of P2Y1 Receptors Causes Anxiolytic-like Effects in the Rat Elevated Plus-maze: Implications for the Involvement of P2Y1 Receptor-Mediated Nitric Oxide Production

Stimulation of P2Y1 Receptors Causes Anxiolytic-like Effects in the Rat Elevated Plus-maze: Implications for the Involvement of P2Y1 Receptor-Mediated Nitric Oxide Production

Anxiolytic Effects of Phosphodiesterase-2 Inhibitors Associated with Increased cGMP Signaling

Antagonism by NOS Inhibition of the Behavioral Effects of Benzodiazepine and GABAA Receptor Agonists in the Mouse Elevated Plus-Maze

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