BDNF Knockdown in the VTA Blocks Social Stress‐Induced Deficits in Social Behavior and Nucleus Accumbens ΔFosB Expression
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. === Social defeat stress, a salient stressor that translates readily from animal studies to humans, alters social approach behavior and indu...
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| Language: | en_US |
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The University of Arizona.
2016
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| Online Access: | http://hdl.handle.net/10150/603650 http://arizona.openrepository.com/arizona/handle/10150/603650 |
| Summary: | 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. === 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. |
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