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

Abstract

Intracerebroventricular injection of stable somatostatin (SST) agonists stimulates food and water intake in rats. We investigated the receptor subtype(s) involved in the dipsogenic effect of intracerebroventricular injection of SST agonists, mechanisms of action, and role. In nonfasted and non-water-deprived male rats with chronic intracerebroventricular cannula, intake of water without food or food without water was monitored separately to avoid any interactions compared with intracerebroventricular vehicle. SST-14 and cortistatin (CST-14) (1 μg/rat icv) increased water intake by 3.1- and 2.7-fold, respectively, while both peptides did not alter food intake at 1 h postinjection in the light phase. By contrast, the stable pan-somatostatin agonist ODT8-SST (1 μg/rat icv) increased both water and food intake by 4.9- and 3.7-fold, respectively. S-346-011, a selective receptor 2 (sst2) agonist (1 μg/rat icv) induced water ingestion, while sst1 or sst4 agonist, injected under the same conditions, did not. The sst2 antagonist S-406-028 (1 μg/rat icv) prevented the 1-h water intake induced by intracerebroventricular ODT8-SST and CST-14. Losartan (100 μg/rat icv), an angiotensin receptor 1 (AT1) antagonist, completely blocked the water consumption induced by intracerebroventricular ODT8-SST, whereas intracerebroventricular injection of S-406-028 did not modify the intracerebroventricular ANG II-induced dipsogenic response. The sst2 antagonist reduced by 40% the increase of the 3-h water intake in the early dark phase. These data indicate that SST-14 and CST-14 interact with sst2 to exert a potent dipsogenic effect, which is mediated downstream by angiotensin-AT1 signaling. These data also indicate that sst2 activation by brain SST-14 and/or CST-14 may play an important role in the regulation of drinking behavior.

Inhibitory effect of somatostatin on insulin secretion is not mediated via the CNS

“…Assuming approximate blood and cerebrospinal fluid (CSF) volumes of distribution of 20 ml and 300 ml, respectively, the predicted concentrations of BIM23014C in blood and CSF will be in the order of 300 nmol/l and 2 mmol/l respectively. This is well above that required to activate SST receptors, including those less preferentially targeted by the agonist (Meyerhof 1998) and similar to doses used in other studies (Rettig et al 1989, Karasawa et al 2014. As shown in Fig.…”

Characterizing the neuropeptide pathways between the forebrain and the pons.

“…To the best of our knowledge the action(s) of CRH and Sst on gustatory neurons in the PBN has not been determined; however, in several other brain regions the influence of CRH on neural activity is predominately excitatory (Blank et al, 2003;Kash et al, 2008;Lowry et al, 2000;Ugolini et al, 2008), while that for Sst is inhibitory (Chieng and Christie, 2010;Connor et al, 2004;Jacquin et al, 1988;Saleh and Cechetto, 1993;Saleh and Cechetto, 1995). Centrally administered CRH has been shown to diminish food intake in a variety of species (Fekete et al, 2007;Jones et al, 1998;Parrott, 1990), while Sst administration increases intake and taste preference (Karasawa et al, 2014;Scalera, 2003;Stengel et al, 2010). Furthermore, injections of CRH into the PBN inhibits sodium appetite, while a CRH receptor antagonist has the opposite effect, increasing sodium chloride intake (Silva et al, 2006).…”

“…Thus, CRH and/or Sst forebrain-PBN pathways, in particular those arising from the BNST and CeA, might be involved in mediating these neurophysiological changes thought to play a role in the elaboration of gustatory preference/aversion and, consequently, ingestive behavior (Grossman et al, 2008;Li et al, 2013a;Moran and Katz, 2014;Shimura et al, 1997a;Shimura et al, 1997c;Tokita et al, 2004). Centrally administered CRH and its homologue urocortin have been shown to diminish intake in a variety of species including rodent, while Sst administration augmented intake (Benoit et al, 2000;Fekete et al, 2007;Heinrichs et al, 1993;Jones et al, 1998;Karasawa et al, 2014;Parrott, 1990;Spina et al, 1996;Stengel et al, 2010). Furthermore, injections of CRH into the lateral PBN inhibits sodium chloride intake in sodium depleted rats, while injections of a CRH receptor antagonist had the opposite effect, increasing sodium chloride intake (Silva et al, 2006).…”

“…The peptides CRH and Sst have centrally mediated actions on autonomic function and ingestive behavior (Benoit et al, 2000;Feifel and Vaccarino, 1990;Feifel and Vaccarino, 1994;Fisher and Brown, 1993;Jones et al, 1998;Karasawa et al, 2014;Scalera, 2003;Spina et al, 1996;Stengel et al, 2010). Although the pathways mediating these effects are not well understood, they likely involve parallel regulation of the flow of gustatory and visceral sensory information to forebrain structures.…”

“…Thus, these specific peptidergic pathways may play an important role in regulating taste responses in the PBN. Both Sst and CRH have been shown to influence food intake and/or taste preference (Bassant et al, 2005;Ciccocioppo et al, 2003;Feifel and Vaccarino, 1990;Feifel and Vaccarino, 1994;Fekete et al, 2007;Heinrichs et al, 1993;Heinrichs and Richard, 1999;Karasawa et al, 2014;Parrott, 1990;Scalera, 2003;Stengel et al, 2010). Indeed, injection of CRH into the PBN disrupts expression of a sodium appetite in rats, while injections of a CRH receptor antagonist had the opposite effect, increasing sodium chloride intake (Silva et al, 2006).…”