Higher susceptibility of somatostatin 4 receptor gene-deleted mice to chronic stress-induced behavioral and neuroendocrine alterations.
The somatostatin 4 receptor (sst4) is widely expressed in stress-related brain areas (e.g. hippocampus, amygdala) and regulates the emotional behavior in acute situations. Since its importance in chronic stress-induced complex pathophysiological alterations is unknown, we investigated the involvement of sst4in the responsiveness to chronic variable stress (CVS). Sstr4 gene-deficient (Sstr4-/-) mice and their wildtype counterparts (Sstr4+/+) were used to examine the behavioral and neuroendocrine alterations as well as chronic neuronal activity (FosB expression) changes in response to CVS. In Sstr4+/+mice, there was no behavioral response to the applied CVS paradigm. In contrast, immobility time in the tail suspension test increased after the CVS in the knockouts. In the forced swim test, Sstr4-/-animals showed increased baseline immobility and then it decreased after the CVS. Light-dark box and open field test behaviors and sucrose preference did not respond to the stress in the knockouts. Adrenal weights increased and thymus weights decreased in both Sstr4+/+and Sstr4-/-mice demonstrating the effect of chronic stress. The relative adrenal weight of stressed knockouts increased to a greater extent, while relative thymus and body weights decreased only in the Sstr4-/-mice. Basal plasma corticosterone concentrations did not change after the CVS in either genotype. FosB immunopositivity in the central and basolateral amygdaloid nuclei was enhanced in stressed knockouts, but not in wild types. This is the first evidence that sst4activation is involved in the behavioral and neuroendocrine alterations induced by chronic stress with a crucial role of plastic changes in the amygdala.
Department of Pharmacology and Pharmacotherapy, University of Pécs Medical School, Pécs, Hungary; János Szentágothai Research Center, University of Pécs, Pécs, Hungary; Center for Neuroscience, University of Pécs Medical School, Pécs, Hungary. Electronic address: scheich.balint@gmail.com.
Bálint
B
Scheich
Department of Pharmacology and Pharmacotherapy, University of Pécs Medical School, Pécs, Hungary; János Szentágothai Research Center, University of Pécs, Pécs, Hungary; Center for Neuroscience, University of Pécs Medical School, Pécs, Hungary. Electronic address: csekoe.kata@gmail.com.
Kata
K
Csekő
Department of Pharmacology and Pharmacotherapy, University of Pécs Medical School, Pécs, Hungary; János Szentágothai Research Center, University of Pécs, Pécs, Hungary; Center for Neuroscience, University of Pécs Medical School, Pécs, Hungary. Electronic address: eva.borbely@aok.pte.hu.
Éva
É
Borbély
János Szentágothai Research Center, University of Pécs, Pécs, Hungary; Center for Neuroscience, University of Pécs Medical School, Pécs, Hungary; Institute of Physiology, University of Pécs Medical School, Pécs, Hungary; MTA-PTE NAP B Molecular Neuroendocrinology Research Group, Hungary. Electronic address: istvan.abraham@aok.pte.hu.
István
I
Ábrahám
Department of Anatomy, University of Pécs Medical School, Pécs, Hungary. Electronic address: valer.csernus@aok.pte.hu.
Valér
V
Csernus
Department of Anatomy, University of Pécs Medical School, Pécs, Hungary; Center for Neuroscience, University of Pécs Medical School, Pécs, Hungary. Electronic address: balazs.b.gaszner@aok.pte.hu.
Balázs
B
Gaszner
Department of Pharmacology and Pharmacotherapy, University of Pécs Medical School, Pécs, Hungary; János Szentágothai Research Center, University of Pécs, Pécs, Hungary; Center for Neuroscience, University of Pécs Medical School, Pécs, Hungary; MTA-PTE NAP B Chronic Pain Research Group, Hungary. Electronic address: zsuzsanna.helyes@aok.pte.hu.
Zsuzsanna
Z
Helyes
D000311:Adrenal Glands / Q000473:pathology; D000679:Amygdala / Q000503:physiopathology; D000818:Animals; D001007:Anxiety / Q000503:physiopathology; D001522:Behavior, Animal; D001921:Brain / Q000503:physiopathology*; D003345:Corticosterone / Q000097:blood; D006624:Hippocampus / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity; D009474:Neurons / Q000378:metabolism; D009490:Neurosecretory Systems / Q000503:physiopathology*; D009929:Organ Size; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000235:genetics / Q000502:physiology*; D013315:Stress, Psychological / Q000503:physiopathology*; D013950:Thymus Gland / Q000473:pathology
D016760:Proto-Oncogene Proteins c-fos; D017481:Receptors, Somatostatin; C098681:somatostatin receptor subtype-4; D003345:Corticosterone
FosB; chronic variable stress; depression; somatostatin; somatostatin 4 receptor