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Adiponectin is critical in determining susceptibility to depressive behaviors and has antidepressant-like activity

Liu, Jing, Guo, Ming, Zhang, Di, Cheng, Shao-Ying, Liu, Meilian, Ding, Jun, Scherer, Philipp E., Liu, Feng, Lu, Xin-Yun
Proceedings of the National Academy of Sciences of the United States of America 2012 v.109 no.30 pp. 12248-12253
adiponectin, animal disease models, behavior disorders, mice, neutralizing antibodies, noninsulin-dependent diabetes mellitus
Depression is a debilitating mental illness and is often comorbid with metabolic disorders such as type 2 diabetes. Adiponectin is an adipocyte–derived hormone with antidiabetic and insulin-sensitizing properties. Here we show that adiponectin levels in plasma are reduced in a chronic social-defeat stress model of depression, which correlates with decreased social interaction time. A reduction in adiponectin levels caused by haploinsufficiency results in increased susceptibility to social aversion, “anhedonia,” and learned helplessness and causes impaired glucocorticoid-mediated negative feedback on the hypothalamic–pituitary–adrenal (HPA) axis. Intracerebroventricular (i.c.v.) injection of an adiponectin neutralizing antibody precipitates stress-induced depressive-like behavior. Conversely, i.c.v. administration of exogenous adiponectin produces antidepressant-like behavioral effects in normal-weight mice and in diet-induced obese diabetic mice. Taken together, these results suggest a critical role of adiponectin in depressive-like behaviors and point to a potential innovative therapeutic approach for depressive disorders.