Somatostatin receptor subtype 4 activation is involved in anxiety and depression-like behavior in mouse models

Bálint Scheich, B. Gaszner, Viktória Kormos, Kristóf László, C. Ádori, Éva Borbély, Zsófia Hajna, Valéria Tékus, K. Bölcskei, István Ábrahám, E. Pintér, J. Szolcsányi, Z. Helyes

Research output: Contribution to journalArticle

13 Citations (Scopus)

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 sst4LacZ 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, sst4LacZ 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.

Original languageEnglish
Pages (from-to)204-215
Number of pages12
JournalNeuropharmacology
Volume101
DOIs
Publication statusPublished - Feb 1 2016

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Hindlimb Suspension
Anxiety
Depression
Septal Nuclei
Anti-Anxiety Agents
Amygdala
Brain
Periaqueductal Gray
Paraventricular Hypothalamic Nucleus
Somatostatin
Mood Disorders
Antidepressive Agents
Immunohistochemistry
Pharmacology
somatostatin receptor subtype-4
(1'S, 2S)-4-amino-N-(1'-carbamoyl-2'-phenylethyl)-2-(4''-methyl-1''-naphthalenesulfonylamino)butanamide

Keywords

  • Anxiety
  • Depression
  • Fos immunohistochemistry
  • Neuropeptides
  • Somatostatin
  • sst receptor

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Somatostatin receptor subtype 4 activation is involved in anxiety and depression-like behavior in mouse models. / Scheich, Bálint; Gaszner, B.; Kormos, Viktória; László, Kristóf; Ádori, C.; Borbély, Éva; Hajna, Zsófia; Tékus, Valéria; Bölcskei, K.; Ábrahám, István; Pintér, E.; Szolcsányi, J.; Helyes, Z.

In: Neuropharmacology, Vol. 101, 01.02.2016, p. 204-215.

Research output: Contribution to journalArticle

Scheich, Bálint ; Gaszner, B. ; Kormos, Viktória ; László, Kristóf ; Ádori, C. ; Borbély, Éva ; Hajna, Zsófia ; Tékus, Valéria ; Bölcskei, K. ; Ábrahám, István ; Pintér, E. ; Szolcsányi, J. ; Helyes, Z. / Somatostatin receptor subtype 4 activation is involved in anxiety and depression-like behavior in mouse models. In: Neuropharmacology. 2016 ; Vol. 101. pp. 204-215.
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