Pattern of Fos expression in the brain induced by selective activation of somatostatin receptor 2 in rats

Central activation of somatostatin (sst) receptors by oligosomatostatin analogs inhibits growth hormone and stress-related rise in catecholamine plasma levels while stimulating grooming, feeding behaviors, gastric transit and acid secretion, which can be mimicked by selective sst2 receptor agonist. To evaluate the pattern of neuronal activation induced by peptide sst receptor agonists, we assessed Fos-expression in rat brain after intracerebroventricular (icv) injection of a newly developed selective sst2 agonist compared to the oligosomatostatin ODT8-SST, a pan-sst1–5 agonist. Ninety min after injection of vehicle (10 μl) or previously established maximal orexigenic dose of peptides (1 μg = 1 nmol/rat), brains were assessed for Fos-immunohistochemistry and doublelabeling. Food and water were removed after injection. The sst2 agonist and ODT8-SST induced a similar Fos distribution pattern except in the arcuate nucleus where only the sst2 agonist increased Fos. Compared to ODT8-SST, the sst2 agonist induced higher Fos-expression by 3.7-times in the basolateral amygdaloid nucleus, 1.2-times in the supraoptic nucleus (SON), 1.6-times in the magnocellular paraventricular hypothalamic nucleus (mPVN), 4.1-times in the external lateral parabrachial nucleus, and 2.6-times in both the inferior olivary nucleus and superficial layer of the caudal spinal trigeminal nucleus. Doublelabeling in the hypothalamus showed that ODT8-SST activates 36% of oxytocin, 63% of vasopressin and 79% of sst2 immunoreactive neurons in the mPVN and 28%, 55% and 25% in the SON, respectively. Selective activation of sst2 receptor results in a more robust neuronal activation than the pan-sst1–5 agonist in various brain regions that may have relevance in sst2 mediated alterations of behavioral, autonomic and endocrine functions.

Research highlights
► ODT8-SST is a pan-sst1-5 receptor agonist.
► The selective sst2 agonist and ODT8-SST induce a similar Fos distribution pattern.
► Activation was found in distinct hypothalamic and brainstem nuclei.
► However, the sst2 agonist induces more robust neuronal activation than ODT8-SST.
► ODT8-SST activates oxytocin, vasopressin and sst2 positive hypothalamic neurons.