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Down-regulation of cholinergic signaling in the habenula induces anhedonia-like behavior.
Han, Seungrie; Yang, Soo Hyun; Kim, Jin Yong; Mo, Seojung; Yang, Esther; Song, Ki Myung; Ham, Byung-Joo; Mechawar, Naguib; Turecki, Gustavo; Lee, Hyun Woo; Kim, Hyun.
Affiliation
  • Han S; Department of Anatomy, College of Medicine, Korea University, Seoul, 136-705, Korea.
  • Yang SH; Department of Anatomy, College of Medicine, Korea University, Seoul, 136-705, Korea.
  • Kim JY; Department of Anatomy, College of Medicine, Korea University, Seoul, 136-705, Korea.
  • Mo S; Department of Anatomy, College of Medicine, Korea University, Seoul, 136-705, Korea.
  • Yang E; Department of Anatomy, College of Medicine, Korea University, Seoul, 136-705, Korea.
  • Song KM; Department of Anatomy, College of Medicine, Korea University, Seoul, 136-705, Korea.
  • Ham BJ; Department of Psychiatry, College of Medicine, Korea University, Seoul, 136-705, Korea.
  • Mechawar N; Department of Psychiatry, McGill University, Douglas Mental Health University Institute, Montreal, QC H4H 1R3, Canada.
  • Turecki G; Department of Psychiatry, McGill University, Douglas Mental Health University Institute, Montreal, QC H4H 1R3, Canada.
  • Lee HW; Department of Anatomy, College of Medicine, Korea University, Seoul, 136-705, Korea. biocais@korea.ac.kr.
  • Kim H; Department of Anatomy, College of Medicine, Korea University, Seoul, 136-705, Korea. kimhyun@korea.ac.kr.
Sci Rep ; 7(1): 900, 2017 04 18.
Article in En | MEDLINE | ID: mdl-28420875
Dysfunction of cholinergic signaling in the brain has long been believed to be associated with depressive disorders. However, the functional impact of habenular cholinergic signaling on the specified depressive behaviors is not well understood. Here, we demonstrated that the expression levels of cholinergic signaling genes (CHAT, VACHT, CHT, CHRNA3, CHRNB3 and CHRNB4) were down-regulated in a chronic restraint stress (CRS) rat model of depression, in which rats display depression-like behaviors such as anhedonia and mood despair. Moreover, knockdown of CHAT in the rat habenula was sufficient to evoke anhedonia-like behavior. The anhedonia-like behavior induced by CHAT knockdown was not reversed by chronic administration of the selective serotonin reuptake inhibitor fluoxetine. To determine whether habenular cholinergic signaling is associated with regulation of dopamine neurons in the ventral tegmental area (VTA) and serotonin neurons in the dorsal raphe nucleus (DRN), we used CHAT::cre transgenic mice expressing the Designer Receptors Exclusively Activated by Designer Drugs (DREADD). Pharmacogenetic activation of habenular cholinergic neurons induces the excitation of dopamine neurons in the VTA and reduces the immunoreactivity of 5-hydroxytryptamine (5-HT) in the DRN. Habenular cholinergic gene down-regulation was recapitulated in the postmortem habenula of suicide victims diagnosed with major depressive disorder (MDD).
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Signal Transduction / Acetylcholine / Receptors, Cholinergic / Habenula / Vesicular Acetylcholine Transport Proteins / Cholinergic Neurons / Anhedonia Limits: Animals / Humans / Male Language: En Journal: Sci Rep Year: 2017 Document type: Article Country of publication: United kingdom

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Signal Transduction / Acetylcholine / Receptors, Cholinergic / Habenula / Vesicular Acetylcholine Transport Proteins / Cholinergic Neurons / Anhedonia Limits: Animals / Humans / Male Language: En Journal: Sci Rep Year: 2017 Document type: Article Country of publication: United kingdom