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

Abstract

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 agonist, ODT8-SST, a pan-sst1–5 agonist. Ninety min after injection of vehicle (10µl) or previously established maximal orexigenic dose of peptides (1µg=1nmol/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-fold in the basolateral amygdaloid nucleus, 1.2-fold in the supraoptic nucleus (SON), 1.6-fold in the magnocellular paraventricular hypothalamic nucleus (mPVN), 4.1-fold in the external lateral parabrachial nucleus, and 2.6-fold 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.

Brain somatostatin receptor 2 mediates the dipsogenic effect of central somatostatin and cortistatin in rats: role in drinking behavior

“…As we reported previously (26), intracerebroventricularly administered ODT8-SST induced a significant c-Fos immunoreactivity in the SON and magnocellular neurons of the PVN (Fig. 6, E and F); however, no clear c-Fos induction was observed in the SFO, MnPO (Fig.…”

“…The procedure was essentially as described in our previous report (26). Briefly, rats were deeply anesthetized with pentobarbital sodium (100 mg/kg ip; Fatal Plus, Vortech Pharmaceuticals, Dearborn, MI) and perfused transcardially with saline followed by ice-cold fixative (4% paraformaldehyde and 14% saturated picric acid in 0.1 M phosphate buffer).…”

Orexigenic response to tail pinch: role of brain NPY1 and corticotropin releasing factor receptors

“…Brains were harvested from rats deeply anesthetized with sodium pentobarbital (70 mg/kg ip, Nembutal, Abbott) after transcardial perfusion and processed as detailed previously (18). Coronal sections (25 m) from the bregma level to the end of the medulla [ϩ2.04 to Ϫ15.96 mm according to Paxinos and Watson's atlas, (41)] were cut using a cryostat (Microm International, Walldorf, Germany).…”

Role of Somatostatin and Somatostatin Receptor type 2 in Postincisional Nociception in Rats

“…Intrathecal administration of SST elicits nociceptive behaviour like caudally directed biting, licking and scratching (Seybold et al, 1982;Pintér et al, 2006). Interestingly, specific sstr2 activation in the brain was observed to lead to more robust neuronal activation than a pan-sstr1-5 agonist (Goebel et al, 2010). Whether intrathecal administration of SST antagonist would have had an antinociceptive effect is an important question considering the fact that SST administration itself could prove neurotoxic (Gaumann and Yaksh, 1988;Mollenholt et al, 1994).…”