title: Roles of Hippocampal Somatostatin Receptor Subtypes in Stress Response and Emotionality.
abstract: 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 sst2or sst4knockout 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 sst2or sst4,but not sst1or sst3receptor agonists produced rapid and sustained inhibition of HPA axis. sst2agonists selectively produced anxiolytic-like behaviors whereas both sst2and sst4agonists 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 sst2and sst4receptors 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 disorders.
authors.affiliation: Institut de Neurosciences Cognitives et Intégratives d'Aquitaine, Avenue des Facultés, Université de Bordeaux, Talence cedex, France.|Centre National de la Recherche Scientifique, UMR 5287, Institut de Neurosciences Cognitives et Intégratives d'Aquitaine, Avenue des Facultés, Talence cedex, France.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Prévôt
authors.affiliation: Institut de Neurosciences Cognitives et Intégratives d'Aquitaine, Avenue des Facultés, Université de Bordeaux, Talence cedex, France.|Centre National de la Recherche Scientifique, UMR 5287, Institut de Neurosciences Cognitives et Intégratives d'Aquitaine, Avenue des Facultés, Talence cedex, France.
authors.forename: François
authors.initials: F
authors.lastname: Gastambide
authors.affiliation: Inserm, UMR 894, Center for Psychiatry &Neuroscience, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Viollet
authors.affiliation: Institut de Neurosciences Cognitives et Intégratives d'Aquitaine, Avenue des Facultés, Université de Bordeaux, Talence cedex, France.|Centre National de la Recherche Scientifique, UMR 5287, Institut de Neurosciences Cognitives et Intégratives d'Aquitaine, Avenue des Facultés, Talence cedex, France.
authors.forename: Nadia
authors.initials: N
authors.lastname: Henkous
authors.affiliation: Inserm, UMR 894, Center for Psychiatry &Neuroscience, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Martel
authors.affiliation: Inserm, UMR 894, Center for Psychiatry &Neuroscience, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Epelbaum
authors.affiliation: Institut de Neurosciences Cognitives et Intégratives d'Aquitaine, Avenue des Facultés, Université de Bordeaux, Talence cedex, France.|Centre National de la Recherche Scientifique, UMR 5287, Institut de Neurosciences Cognitives et Intégratives d'Aquitaine, Avenue des Facultés, Talence cedex, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Béracochéa
authors.affiliation: Institut de Neurosciences Cognitives et Intégratives d'Aquitaine, Avenue des Facultés, Université de Bordeaux, Talence cedex, France.|Centre National de la Recherche Scientifique, UMR 5287, Institut de Neurosciences Cognitives et Intégratives d'Aquitaine, Avenue des Facultés, Talence cedex, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Guillou
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D000928:Antidepressive Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D003345:Corticosterone / Q000097:blood / Q000378:metabolism; D004644:Emotions / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D015282:Octreotide / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000187:drug effects; D017481:Receptors, Somatostatin / Q000819:agonists / Q000235:genetics / Q000502:physiology*; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology; D013315:Stress, Psychological / Q000503:physiopathology*
chemical_list: D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D017481:Receptors, Somatostatin; C051458:vapreotide; D013004:Somatostatin; D015282:Octreotide; D003345:Corticosterone