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Augmentation of the NO-cGMP cascade induces anxiogenic-like effect in mice

100%

Volke V., Wegener G., Vasar E.

Journal of Physiology and Pharmacology

2003

tom 54

nr 4

Several studies have reported the anxiolytic-like effects of various nitric oxide synthase inhibitors in distinct animal models. However, in the context of anxiety, the possible involvement of cyclic GMP, believed to be one of the main targets of NO, remains obscure. Cyclic GMP is degraded by the specific phosphodiesterases in the brain. Therefore, we studied the effect of the selective phosphodiesterase type 5 inhibitor sildenafil in the mouse elevated plus-maze test of anxiety and in the open field test of locomotion. We found that sildenafil (0.05-10 mg/kg i.p.) alone did not affect the behavior of animals in the plus-maze or open field tests, but the anxiogenic beta-carboline DMCM given in a subconvulsive dose (2 mg/kg i.p.) decreased the time spent on open arms in the elevated plus-maze. Treatment with the NO precursor L-arginine (200 mg/kg i.p.) did not modify the behavior of animals in the plus-maze, however, when sildenafil (1 mg/kg i.p.) was administered in combination with L-arginine (200 mg/kg i.p.), both the time spent on the open arms and the percentage of open arm visits were significantly decreased. We conclude that augmentation of the NO-cGMP cascade induces anxiogenic-like effect in mice.

Combined chronic treatment with citalopram and lithium does not modify the regional neurochemistry of nitric oxide in rat brain

76%

Wegener G., Bandpey Z., Heiberg I. L., Volke V., Trabace L., Rosenberg R., Harvey B. H.

Journal of Physiology and Pharmacology

2004

tom 55

nr 3

A substantial number of patients do not respond sufficiently to antidepressant drugs and are therefore often co-medicated with lithium as an augmentation strategy. Also inhibitors of nitric oxide synthase (NOS) have been used as an augmentation strategy, while inhibitors of NOS exhibit antidepressant-like properties in various animal models. Therefore, we hypothesized that modulation of NOS may be involved in the long-term effects of antidepressants and lithium, and studied the influence of acute and chronic administration of citalopram, alone or in combination with lithium, on NOS activity in hippocampus, cerebellum, and frontal cortex, by determination of L-citrulline being formed. We found that administration of acute or chronic citalopram (5 mg/kg and 20 mg/kg/24h, respectively) alone or in combination with subchronic lithium (60 mmol/kg chow pellet) did not influence the activity of NOS ex vivo in all regions compared to control. In contrast, high doses of lithium caused a significant decrease in NOS activity in vitro. We conclude that basal conditions are unsuitable for the study of antidepressant effects on NOS, and that the neurochemistry of nitric oxide remains unaltered following chronic citalopram or subchronic lithium under normal physiological conditions.

Ograniczanie wyników

2 Journal of Physiology and Pharmacology

2 Volke V.

2 Wegener G.

1 Bandpey Z.

1 Harvey B. H.

1 Heiberg I. L.

1 Rosenberg R.

1 Trabace L.

1 Vasar E.

1 2004

1 2003

Wyniki wyszukiwania

Augmentation of the NO-cGMP cascade induces anxiogenic-like effect in mice

Combined chronic treatment with citalopram and lithium does not modify the regional neurochemistry of nitric oxide in rat brain