Viral depletion of VTA BDNF in rats modulates social behavior, consequences of intermittent social defeat stress, and long-term weight regulation

NEUROSCIENCE LETTERS

卷:502

Article

Fanous, Sanya^1,2  Terwilliger, Ernest F.⁵  Hammer, Ronald P., Jr.^1,2,3,4  Nikulina, Ella M.^1,2 

[1] Tufts Univ, Sch Med, Dept Pharmacol, Boston, MA 02111 USA

[2] Univ Arizona, Coll Med, Dept Basic Med Sci, Phoenix, AZ 85004 USA

[3] Univ Arizona, Dept Pharmacol, Phoenix, AZ 85004 USA

[4] Univ Arizona, Dept Psychiat, Phoenix, AZ 85004 USA

[5] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA

关键词: Ventral tegmental area;    Brain-derived neurotrophic factor;    Mesolimbic;    Feeding;    Dopamine;    Weight;   

DOI  :  10.1016/j.neulet.2011.07.043

来源: Elsevier

【 摘 要 】

Mesolimbic brain-derived neurotrophic factor (BDNF) is implicated in sustained behavioral changes following chronic social stress, and its depletion may reduce susceptibility to such behavioral alterations. Enhanced mesolimbic BDNF is proposed as pro-depressive and anhedonic, while depleting ventral tegmetal area (VTA) BDNF increases weight by enhancing hedonic eating. Here, we questioned whether depletion of VTA BDNF would alleviate social defeat stress-induced deficits in weight regulation, or affect social behavior in the presence or absence of social stress. Male Sprague-Dawley rats received bilateral intra-VTA infusions of adeno-associated virus (AAV) vectors containing shRNA against BDNF or a control virus. Three weeks later, rats underwent 4 episodes of social defeat stress involving exposure to an aggressive Long-Evans resident rat, or control handling every third day. Depleted VTA BDNF conferred resistance to the deficient weight regulation normally observed during intermittent social defeat stress, and enhanced long-term weight gain regardless of stress history. In addition, social approach and avoidance behavior towards a novel social target were measured 7 weeks after stress. Social defeat stress chronically reduced social behavior, whereas depletion of VTA BDNF chronically increased social behavior. Our results reveal that depletion of VTA BDNF alleviates some consequences of intermittent social defeat stress, enhances social behavior, and may contribute to weight gain. These data implicate VTA BDNF in protracted behavioral responses to stress, social stimuli, and weight regulation. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

【 授权许可】

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