Role of ventral hippocampal nitric oxide/cGMP pathway in anxiety-related behaviors in rats submitted to the elevated T-maze.

The L-arginine/nitric oxide (NO)/cGMP pathways have been implicated in the control of a variety of physiological mechanisms and are believed to participate in the modulation of anxiety in the CNS. The aim of this study was to investigate the effects of N(G)-nitro-L-arginine-methyl-ester (L-NAME), a non-selective inhibitor of NO synthase (NOS); 7-nitroindazole (7-NI), a preferential inhibitor of neuronal NOS; and sodium nitroprusside (SNP), an NO donor, administered into the ventral hippocampus (VH) of rats submitted to the elevated T-maze (ETM). The ETM, an animal model derived from the elevated plus-maze, allows the measurement of two defensive behavioral responses in the same rat: inhibitory avoidance and escape. Results showed that L-NAME and 7-NI impaired the acquisition of inhibitory avoidance and prolonged escape latency in the ETM, suggesting an anxiolytic-like and panicolytic-like effect, respectively. SNP facilitated the acquisition of inhibitory avoidance without interfering with escape performance, suggesting an anxiogenic-like effect. Treatment with methylene blue did not alter per se any of the behavioral responses measured in the ETM, but blocked the effect promoted by SNP. Thus, altogether these results suggest that NO in the VH is critically involved in the modulation of defensive behavior of rats exposed to the ETM.