Decreased nucleus accumbens expression of psychiatric disorder risk gene Cacna1c promotes susceptibility to social stress
JournalInternational Journal of Neuropsychopharmacology
PublisherOxford University Press
MetadataShow full item record
AbstractBackground: Polymorphisms in the CACNA1C gene are associated with human mood disorders. The rodent social defeat model of stress/mood-disorder susceptibility results in maladaptive consequences mediated by altered function of mesolimbic circuits. Methods: mRNA levels of Cacna1c in the nucleus accumbens of mice exposed to social defeat were assessed. Cacna1c was selectively deleted in the nucleus accumbens of floxed Cacna1c mice using viral Cre-recombinase to examine Cacna1c in social defeat susceptibility. Results: Reduced expression of Cacan1c in the nucleus accumbens is associated with increased susceptibility to social defeat stress, and a knockdown of Cacna1c in the nucleus accumbens significantly increases susceptibility measured by social interaction and female urine preference. Conclusions: Cacna1c reduction causally predisposes to the maladaptive outcomes of social stress. Normal Cacna1c function in the nucleus accumbens is crucial for resiliency to social stressors. Variations in expression of CACNA1C in the nucleus accumbens may mediate human risk for developing mood disorders and be a target for therapeutic intervention. Copyright The Author 2017.
SponsorsThis study was supported by US NIH grant MH103847 and Brain & Behavior Research Foundation Independent Investigator Award 20230 to T.D.G.
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85026474334&doi=10.1093%2fijnp%2fpyw112&partnerID=40&md5=f563555c6eaa6b3e8198d3988dfd4b3e; http://hdl.handle.net/10713/11337
- Reduced Slc6a15 in Nucleus Accumbens D2-Neurons Underlies Stress Susceptibility.
- Authors: Chandra R, Francis TC, Nam H, Riggs LM, Engeln M, Rudzinskas S, Konkalmatt P, Russo SJ, Turecki G, Iniguez SD, Lobo MK
- Issue date: 2017 Jul 5
- Cell-Type-Specific Epigenetic Editing at the Fosb Gene Controls Susceptibility to Social Defeat Stress.
- Authors: Hamilton PJ, Burek DJ, Lombroso SI, Neve RL, Robison AJ, Nestler EJ, Heller EA
- Issue date: 2018 Jan
- Reduced levels of Cacna1c attenuate mesolimbic dopamine system function.
- Authors: Terrillion CE, Dao DT, Cachope R, Lobo MK, Puche AC, Cheer JF, Gould TD
- Issue date: 2017 Jun
- A novel role of the WNT-dishevelled-GSK3β signaling cascade in the mouse nucleus accumbens in a social defeat model of depression.
- Authors: Wilkinson MB, Dias C, Magida J, Mazei-Robison M, Lobo M, Kennedy P, Dietz D, Covington H 3rd, Russo S, Neve R, Ghose S, Tamminga C, Nestler EJ
- Issue date: 2011 Jun 22
- SIRT1 Mediates Depression-Like Behaviors in the Nucleus Accumbens.
- Authors: Kim HD, Hesterman J, Call T, Magazu S, Keeley E, Armenta K, Kronman H, Neve RL, Nestler EJ, Ferguson D
- Issue date: 2016 Aug 10