Roles of Hippocampal Somatostatin Receptor Subtypes in Stress Response and Emotionality.
Neuropsychopharmacol. 2016-12-16; 42(8): 1647-1656
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Prévôt TD(1)(2), Gastambide F(1)(2), Viollet C(3)(4), Henkous N(1)(2), Martel G(3)(4), Epelbaum J(3)(4), Béracochéa D(1)(2), Guillou JL(1)(2).
(1)Institut de Neurosciences Cognitives et Intégratives d’Aquitaine, Avenue des Facultés, Université de Bordeaux, Talence cedex, France.
(2)Centre National de la Recherche Scientifique, UMR 5287, Institut de Neurosciences Cognitives et Intégratives d’Aquitaine, Avenue des Facultés, Talence cedex, France.
(3)Inserm, UMR 894, Center for Psychiatry &Neuroscience, Paris, France.
(4)Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
Altered brain somatostatin functions recently appeared as key elements for the
pathogenesis of stress-related neuropsychiatric disorders. The hippocampus exerts
an inhibitory feedback on stress but the mechanisms involved remain unclear. We
investigated herein the role of hippocampal somatostatin receptor subtypes in
both stress response and behavioral emotionality using C57BL/6, wild type and
sst2 or sst4 knockout mice. Inhibitory effects of hippocampal infusions of
somatostatin agonists on stress-induced hypothalamo-pituitary-adrenal axis (HPA)
activity were tested by monitoring peripheral blood and local hippocampus
corticosterone levels, the latter by using microdialysis. Anxiolytic and
antidepressant-like effects were determined in the elevated-plus maze, open
field, forced swimming, and stress-sensitive beam walking tests. Hippocampal
injections of somatostatin analogs and sst2 or sst4, but not sst1 or sst3
receptor agonists produced rapid and sustained inhibition of HPA axis. sst2
agonists selectively produced anxiolytic-like behaviors whereas both sst2 and
sst4 agonists had antidepressant-like effects. Consistent with these findings,
high corticosterone levels and anxiety were found in sst2KO mice and
depressive-like behaviors observed in both sst2KO and sst4KO strains. Both
hippocampal sst2 and sst4 receptors selectively inhibit stress-induced HPA axis
activation but mediate anxiolytic and antidepressive effects through distinct
mechanisms. Such results are to be accounted for in development of
pathway-specific somatostatin receptor agents in the treatment of
hypercortisolism (Cushing’s disease) and stress-related neuropsychiatric
PMID: 27986975 [Indexed for MEDLINE]