The anxiolytic effects of somatostatin following intra-septal and intra-amygdalar microinfusions are reversed by the selective sst2 antagonist PRL2903

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Abstract

Somatostatin (SST) is a polypeptide with two biological isoforms (SST14, and SST28), and five SST receptor subtypes (sst1-5). Together, they mediate a number of neural and hormonal functions. Recently, we found that intracerebroventricular (ICV), intra-amygdalar, and intra-septal microinfusions of SST14, SST28, and a selective sst2 receptor agonist L-779976 all produced anxiolytic-like effects in the elevated plus-maze, a widely used animal model of anxiety. The receptor specificity of these anxiolytic-like effects, however, has not been conclusively established.

Accordingly, the anxiolytic effects of SST in the elevated plus-maze were assessed following intra-septal or intra-amygalar microinfusions of 1) SST (1.5 μg per hemisphere), 2) the highly selective sst2 receptor antagonist PRL2903 (1.5 μg per hemisphere), or 3) the combination of SST and PRL2903 (each 1.5 μg per hemisphere). Antagonism of the anxiolytic effects of SST in the plus-maze by PRL2903 should result in open-arm exploration that is equivalent to that of 4) vehicle-injected control rats.

Both intra-septal and intra-amygdalar microinfusions of SST produced anxiolytic effects in the elevated plus-maze, consistent with results found previously after ICV microinfusions (see Engin et al., 2008; Engin and Treit, 2009; Yeung et al., 2011). More importantly, infusion of PRL2903 completely reversed the anxiolytic effects of SST in both the amygdala and the septum. These results show that somatostatin's anxiolytic effects are mediated by sst2 receptors contained in the amygdala and septum of the rat brain.

Highlights

▸ Somatostatin [SST] mediates its central functions through receptors sst1-5. ▸ Intra-amygdalar or intra-septal infusion of SST reduced anxiety in the plus-maze. ▸ PRL2903, a selective sst2 antagonist, reversed these anxiolytic effects of SST. ▸ These findings suggest sst2 receptors in the amygdala and septum mediate anxiety.

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