Abstract

Somatostatin (SST) isoforms, SST 14 and SST 28, inhibit regulatory hormones in the periphery (e.g., growth hormone) and are widely distributed in the brain. In recent experiments, intracerebroventricular (ICV) SST produced anxiolytic-like effects in both behavioral and electrophysiological models. The sites of action of these anxiolytic effects in the brain, however, and the relative contributions of SST 14 and SST 28 to these effects are unknown. Anxiolytic effects were assessed in the plus-maze and shock-probe tests after (1) intra-amygdalar microinfusion of SST 14 (0.5 or 3 μg per hemisphere) or SST 28 (3 μg per hemisphere), (2) intra-septal microinfusion of SST 14 (0.5 or 1.5 μg per hemisphere) or SST 28 (1.5 μg per hemisphere), or (3) intra-striatal microinfusion of SST 14 (3 μg per hemisphere). Intra-amygdalar and intra-septal microinfusions of SST 14 and SST 28 produced robust anxiolytic-like effects in the behavioral tests, unlike intra-striatal microinfusions. The magnitude of the anxiolytic effects in the amygdala and septum were comparable to those found previously with ICV SST 14, ICV L-779976, an SST (sst2) receptor agonist, and ICV diazepam, a classical benzodiazepine anxiolytic. SST receptors in the septum and amygdala are responsive to both SST 14 and SST 28, but not those in the striatum. Although no obvious differences in the anxiolytic-like effects of the isoforms were detected, quantitative or even qualitative differences in their specific anxiolytic effects may occur in different sub-regions of the septum and amygdala, as has been found for benzodiazepine anxiolytics.

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