title: Somatostatin receptor subtype 4 activation is involved in anxiety and depression-like behavior in mouse models.
abstract: Somatostatin regulates stress-related behavior and its expression is altered in mood disorders. However, little is known about the underlying mechanisms, especially about the importance of its receptors (sst1-sst5) in anxiety and depression-like behavior. Here we analyzed the potential role of sst4 receptor in these processes, since sst4 is present in stress-related brain regions, but there are no data about its functional relevance. Genetic deletion of sst4 (Sstr4(-/-)) and its pharmacological activation with the newly developed selective non-peptide agonist J-2156 were used. Anxiety was examined in the elevated plus maze (EPM) and depression-like behavior in the forced swim (FST) and tail suspension tests (TST). Neuronal activation during the TST was monitored by Fos immunohistochemistry, receptor expression was identified by sst4(LacZ) immunostaining in several brain regions. Sstr4(-/-) mice showed increased anxiety in the EPM and enhanced depression-like behavior in the FST. J-2156 (100 μg/kg i.p.) exhibited anxiolytic effect in the EPM and decreased immobility in the TST. J-2156 alone did not influence Fos immunoreactivity in intact mice, but significantly increased the stress-induced Fos response in the dorsal raphe nucleus, central projecting Edinger-Westphal nucleus, periaqueductal gray matter, the magnocellular, but not the parvocellular part of the hypothalamic paraventricular nucleus, lateral septum, bed nucleus of the stria terminalis and the amygdala. Notably, sst4(LacZ) immunoreactivity occurred in the central and basolateral amygdala. Together, these studies reveal that sst4 mediates anxiolytic and antidepressant-like effects by enhancing the stress-responsiveness of several brain regions with special emphasis on the amygdala.
authors.affiliation: Department of Pharmacology and Pharmacotherapy, University of Pécs Medical School, H-7624 Pécs, Hungary; János Szentágothai Research Centre, University of Pécs, H-7624 Pécs, Hungary; Centre for Neuroscience, University of Pécs Medical School, H-7624 Pécs, Hungary. Electronic address: scheich.balint@gmail.com.
authors.forename: Bálint
authors.initials: B
authors.lastname: Scheich
authors.affiliation: Department of Anatomy, University of Pécs Medical School, H-7624 Pécs, Hungary; Centre for Neuroscience, University of Pécs Medical School, H-7624 Pécs, Hungary. Electronic address: balazs.b.gaszner@aok.pte.hu.
authors.forename: Balázs
authors.initials: B
authors.lastname: Gaszner
authors.affiliation: Department of Pharmacology and Pharmacotherapy, University of Pécs Medical School, H-7624 Pécs, Hungary; János Szentágothai Research Centre, University of Pécs, H-7624 Pécs, Hungary; Centre for Neuroscience, University of Pécs Medical School, H-7624 Pécs, Hungary. Electronic address: viktoria.kormos@gmail.com.
authors.forename: Viktória
authors.initials: V
authors.lastname: Kormos
authors.affiliation: Department of Physiology, University of Pécs Medical School, H-7624 Pécs, Hungary; Centre for Neuroscience, University of Pécs Medical School, H-7624 Pécs, Hungary. Electronic address: kristof.laszlo@aok.pte.hu.
authors.forename: Kristóf
authors.initials: K
authors.lastname: László
authors.affiliation: Department of Neuroscience, Karolinska Institutet, SE-17177 Stockholm, Sweden. Electronic address: csaba.adori@ki.se.
authors.forename: Csaba
authors.initials: C
authors.lastname: Ádori
authors.affiliation: Department of Pharmacology and Pharmacotherapy, University of Pécs Medical School, H-7624 Pécs, Hungary; János Szentágothai Research Centre, University of Pécs, H-7624 Pécs, Hungary; Centre for Neuroscience, University of Pécs Medical School, H-7624 Pécs, Hungary. Electronic address: eva.borbely@aok.pte.hu.
authors.forename: Éva
authors.initials: É
authors.lastname: Borbély
authors.affiliation: Department of Pharmacology and Pharmacotherapy, University of Pécs Medical School, H-7624 Pécs, Hungary; János Szentágothai Research Centre, University of Pécs, H-7624 Pécs, Hungary; Centre for Neuroscience, University of Pécs Medical School, H-7624 Pécs, Hungary. Electronic address: zsofia.hajna@aok.pte.hu.
authors.forename: Zsófia
authors.initials: Z
authors.lastname: Hajna
authors.affiliation: Department of Pharmacology and Pharmacotherapy, University of Pécs Medical School, H-7624 Pécs, Hungary; János Szentágothai Research Centre, University of Pécs, H-7624 Pécs, Hungary; Centre for Neuroscience, University of Pécs Medical School, H-7624 Pécs, Hungary. Electronic address: valeria.tekus@aok.pte.hu.
authors.forename: Valéria
authors.initials: V
authors.lastname: Tékus
authors.affiliation: Department of Pharmacology and Pharmacotherapy, University of Pécs Medical School, H-7624 Pécs, Hungary; János Szentágothai Research Centre, University of Pécs, H-7624 Pécs, Hungary; Centre for Neuroscience, University of Pécs Medical School, H-7624 Pécs, Hungary. Electronic address: kata.bolcskei@aok.pte.hu.
authors.forename: Kata
authors.initials: K
authors.lastname: Bölcskei
authors.affiliation: János Szentágothai Research Centre, University of Pécs, H-7624 Pécs, Hungary; Department of Physiology, University of Pécs Medical School, H-7624 Pécs, Hungary; Centre for Neuroscience, University of Pécs Medical School, H-7624 Pécs, Hungary. Electronic address: istvan.abraham@aok.pte.hu.
authors.forename: István
authors.initials: I
authors.lastname: Ábrahám
authors.affiliation: Department of Pharmacology and Pharmacotherapy, University of Pécs Medical School, H-7624 Pécs, Hungary; János Szentágothai Research Centre, University of Pécs, H-7624 Pécs, Hungary; PharmInVivo Ltd., H-7624 Pécs, Hungary; Centre for Neuroscience, University of Pécs Medical School, H-7624 Pécs, Hungary. Electronic address: erika.pinter@aok.pte.hu.
authors.forename: Erika
authors.initials: E
authors.lastname: Pintér
authors.affiliation: Department of Pharmacology and Pharmacotherapy, University of Pécs Medical School, H-7624 Pécs, Hungary; János Szentágothai Research Centre, University of Pécs, H-7624 Pécs, Hungary; PharmInVivo Ltd., H-7624 Pécs, Hungary; Centre for Neuroscience, University of Pécs Medical School, H-7624 Pécs, Hungary. Electronic address: janos.szolcsanyi@aok.pte.hu.
authors.forename: János
authors.initials: J
authors.lastname: Szolcsányi
authors.affiliation: Department of Pharmacology and Pharmacotherapy, University of Pécs Medical School, H-7624 Pécs, Hungary; János Szentágothai Research Centre, University of Pécs, H-7624 Pécs, Hungary; PharmInVivo Ltd., H-7624 Pécs, Hungary; Centre for Neuroscience, University of Pécs Medical School, H-7624 Pécs, Hungary; MTA-PTE NAP B Pain Research Group, H-7624 Pécs, Hungary. Electronic address: zsuzsanna.helyes@aok.pte.hu.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Helyes
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001007:Anxiety / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002073:Butanes / Q000494:pharmacology / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D019417:Hindlimb Suspension; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009281:Naphthalenes / Q000494:pharmacology / Q000627:therapeutic use*; D016761:Oncogene Proteins v-fos / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000235:genetics / Q000378:metabolism*; D013450:Sulfones / Q000494:pharmacology / Q000627:therapeutic use*; D013550:Swimming / Q000523:psychology
chemical_list: D000928:Antidepressive Agents; D002073:Butanes; D009281:Naphthalenes; D016761:Oncogene Proteins v-fos; D017481:Receptors, Somatostatin; D013450:Sulfones; C098681:somatostatin receptor subtype-4; C499293:(1'S, 2S)-4-amino-N-(1'-carbamoyl-2'-phenylethyl)-2-(4''-methyl-1''-naphthalenesulfonylamino)butanamide
keywords: Anxiety; Depression; Fos immunohistochemistry; Neuropeptides; Somatostatin; sst(4) receptor