BDNF Knockdown in the VTA Blocks Social Stress‐Induced Deficits in Social Behavior and Nucleus Accumbens ΔFosB Expression

Persistent Link:
http://hdl.handle.net/10150/603650
Title:
BDNF Knockdown in the VTA Blocks Social Stress‐Induced Deficits in Social Behavior and Nucleus Accumbens ΔFosB Expression
Author:
Hakes, Emelia
Affiliation:
The University of Arizona College of Medicine - Phoenix
Issue Date:
25-Mar-2016
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the College of Medicine - Phoenix, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Collection Information:
This item is part of the College of Medicine - Phoenix Scholarly Projects 2016 collection. For more information, contact the Phoenix Biomedical Campus Library at pbc-library@email.arizona.edu.
Publisher:
The University of Arizona.
Abstract:
Social defeat stress, a salient stressor that translates readily from animal studies to humans, alters social approach behavior and induces brain‐derived neurotrophic factor (BDNF) in the ventral tegmental area (VTA), as well as the stable transcription factor, ΔFosB, in the nucleus accumbens (NAc) of rats. However, it is unknown whether VTA BDNF is required for these effects of stress. Rats underwent stereotaxic surgery to receive bilateral intra‐VTA infusions of adeno‐associated virus inducing green fluorescent protein (AAV‐GFP) or GFP and short hairpin RNA directed against BDNF (shRNA‐BDNF). Following recovery, rats were subjected to control handling or social defeat stress, consisting of a brief confrontation between an aggressive resident and an experimental intruder rat every third day for 10 days. Social interaction was assessed in a social approach assay two weeks later. Following perfusion, brains were removed and processed for immunohistochemical analysis of ΔFosB expression. VTA BDNF knockdown attenuated the effect of social stress on weight gain, and increased social approach behavior, which is normally reduced by social stress. Furthermore, social stress increased NAc ΔFosB labeling in AAV‐GFP rats, but this effect was blocked by prior shRNA‐BDNF treatment. This study further implicates VTA BDNF signaling in the effects of stress on social behavior. VTA BDNF appears to be required for the long‐lasting effects of social stress on ΔFosB expression in the NAc. Thus, activation of BDNF signaling in mesolimbic circuits may underlie the persistent deficits of social behavior induced by stress exposure in some individuals.
MeSH Subjects:
Social Behavior; Nucleus Accumbens; Brain‐derived Neurotrophic Factor; Ventral Tegmental Area
Description:
A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine.
Mentor:
Hammer, Jr., Ron PhD; Nikulina, Ella PhD

Full metadata record

DC FieldValue Language
dc.language.isoen_USen
dc.titleBDNF Knockdown in the VTA Blocks Social Stress‐Induced Deficits in Social Behavior and Nucleus Accumbens ΔFosB Expressionen_US
dc.contributor.authorHakes, Emeliaen
dc.contributor.departmentThe University of Arizona College of Medicine - Phoenixen
dc.date.issued2016-03-25en
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the College of Medicine - Phoenix, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.collectioninformationThis item is part of the College of Medicine - Phoenix Scholarly Projects 2016 collection. For more information, contact the Phoenix Biomedical Campus Library at pbc-library@email.arizona.edu.en_US
dc.publisherThe University of Arizona.en
dc.description.abstractSocial defeat stress, a salient stressor that translates readily from animal studies to humans, alters social approach behavior and induces brain‐derived neurotrophic factor (BDNF) in the ventral tegmental area (VTA), as well as the stable transcription factor, ΔFosB, in the nucleus accumbens (NAc) of rats. However, it is unknown whether VTA BDNF is required for these effects of stress. Rats underwent stereotaxic surgery to receive bilateral intra‐VTA infusions of adeno‐associated virus inducing green fluorescent protein (AAV‐GFP) or GFP and short hairpin RNA directed against BDNF (shRNA‐BDNF). Following recovery, rats were subjected to control handling or social defeat stress, consisting of a brief confrontation between an aggressive resident and an experimental intruder rat every third day for 10 days. Social interaction was assessed in a social approach assay two weeks later. Following perfusion, brains were removed and processed for immunohistochemical analysis of ΔFosB expression. VTA BDNF knockdown attenuated the effect of social stress on weight gain, and increased social approach behavior, which is normally reduced by social stress. Furthermore, social stress increased NAc ΔFosB labeling in AAV‐GFP rats, but this effect was blocked by prior shRNA‐BDNF treatment. This study further implicates VTA BDNF signaling in the effects of stress on social behavior. VTA BDNF appears to be required for the long‐lasting effects of social stress on ΔFosB expression in the NAc. Thus, activation of BDNF signaling in mesolimbic circuits may underlie the persistent deficits of social behavior induced by stress exposure in some individuals.en
dc.typeThesisen
dc.subject.meshSocial Behavioren
dc.subject.meshNucleus Accumbensen
dc.subject.meshBrain‐derived Neurotrophic Factoren
dc.subject.meshVentral Tegmental Areaen
dc.descriptionA Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine.en
dc.contributor.mentorHammer, Jr., Ron PhDen
dc.contributor.mentorNikulina, Ella PhDen
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