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Cell DOI:10.1016/j.cell.2018.03.037

The Neuropeptide Tac2 Controls a Distributed Brain State Induced by Chronic Social Isolation Stress.

Publication TypeJournal Article
Year of Publication2018
AuthorsZelikowsky, M, Hui, M, Karigo, T, Choe, A, Yang, B, Blanco, MR, Beadle, K, Gradinaru, V, Deverman, BE, Anderson, DJ
Date Published2018 05 17
KeywordsAnimals, Antipsychotic Agents, Behavior, Animal, Brain, Female, Genetic Vectors, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Neurokinin B, Neurons, Protein Isoforms, Protein Precursors, Receptors, Tachykinin, RNA Interference, RNA, Small Interfering, Social Isolation, Stress, Psychological, Tachykinins, Up-Regulation

Chronic social isolation causes severe psychological effects in humans, but their neural bases remain poorly understood. 2 weeks (but not 24 hr) of social isolation stress (SIS) caused multiple behavioral changes in mice and induced brain-wide upregulation of the neuropeptide tachykinin 2 (Tac2)/neurokinin B (NkB). Systemic administration of an Nk3R antagonist prevented virtually all of the behavioral effects of chronic SIS. Conversely, enhancing NkB expression and release phenocopied SIS in group-housed mice, promoting aggression and converting stimulus-locked defensive behaviors to persistent responses. Multiplexed analysis of Tac2/NkB function in multiple brain areas revealed dissociable, region-specific requirements for both the peptide and its receptor in different SIS-induced behavioral changes. Thus, Tac2 coordinates a pleiotropic brain state caused by SIS via a distributed mode of action. These data reveal the profound effects of prolonged social isolation on brain chemistry and function and suggest potential new therapeutic applications for Nk3R antagonists.


Alternate JournalCell
PubMed ID29775595
PubMed Central IDPMC5967263
Grant ListK99 MH108734 / MH / NIMH NIH HHS / United States
R01 MH070053 / MH / NIMH NIH HHS / United States
R01 MH085082 / MH / NIMH NIH HHS / United States
R01 MH112593 / MH / NIMH NIH HHS / United States
/ HHMI / Howard Hughes Medical Institute / United States