Anxiolytic and antidepressant actions of somatostatin: the role of sst2 and sst3 receptors

Somatostatin is a cyclic polypeptide that inhibits the release of a variety of regulatory hormones (e.g., growth hormone, insulin, glucagon, and thyrotropin). Somatostatin is also widely distributed within the central nervous system (CNS), acting both as a neurotransmitter and as a neuromodulator. Recently, we showed that intracerebroventricular (i.c.v.) administration of somatostatin reduced anxiety-like and depression-like behaviors in animal models. The somatostatin receptor subtypes that are involved in these behavioral effects, however, have not been investigated. In the CNS, the neurotransmitter actions of somatostatin are mediated through five G-protein coupled receptors (sst1 to sst5). We examined the behavioral effects of i.c.v. microinfusions of different doses of selective agonists of each of the five somatostatin receptor subtypes. Their behavioral effects were assessed in the elevated plus-maze and the forced swim apparatus, rodent models of anxiolytic and antidepressant drug effects, respectively. Anxiety-like behavior was reduced following i.c.v. infusions of a selective sst2 receptor agonist, but not after infusions of the other four receptor agonists. An antidepressant-like effect was observed following infusions of either sst2 or sst3 agonists. The results add to our nascent understanding of the role of somatostatin in anxiety- and depression-like behavior and suggest a clinical role for somatostatin agonists for the simultaneous treatment of anxiety and depression, which are often comorbid.