Involvement of the GABAergic and the serotonergic systems in the anxiolytic effects expressed by the nitric oxide (NO) donor sodium nitroprusside (SNP) in the male rat

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Abstract
Rationale: Anxiety is a chronic severe psychiatric disorder. In a series of studies, the implication of the gaseous molecule nitric oxide (NO) in anxiety has been evidenced. Further, the outcome of preclinical research suggests that different NO donors, including sodium nitroprusside (SNP), have expressed an anxiolytic profile revealed in animal models of anxiety. Regardless of this, it is not yet clarified the mechanism(s) of action by which SNP induces its beneficial effects on anxiety. In this context, it has been hypothesized that these effects might be attributed to a potential interaction of this NO donor with the GABA type A and the 5-HT1A serotonergic receptors. Objectives: The current study was designed to investigate this issue in the male rat. Methods: To this end, the light/dark box and the open field tests were utilized. Results: SNP (1 mg/kg, i.p.) applied acutely induced an anti-anxiety-like effect evidenced either in the light/dark box or in the open field test. Either the GABAA receptor antagonist flumazenil (10 mg/kg, i.p.) or the 5-HT1A serotonin receptor agonist 8-OH-DPAT (0.25 mg/kg, i.p.) suppressed the above reported anxiolytic effects of SNP. Conclusions: The results here reported propose a functional interaction between SNP with the GABAergic and the serotonergic systems on anxiety and thus, might offer a plausible explanation for SNP’s anxiolytic effects.

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