role of the amygdala in antidepressant effects on hippocampal cell proliferation and survival and on depression-like behavior in the rat杏仁核的作用抗抑郁作用海马细胞增殖和生存和类似抑郁大鼠行为.pdfVIP

Role of the Amygdala in Antidepressant Effects on Hippocampal Cell Proliferation and Survival and on Depression-like Behavior in the Rat ´ Jorge E. Castro, Emilio Varea, Cristina Marquez, Maria Isabel Cordero, Guillaume Poirier, Carmen Sandi* ´ ´ ´ Laboratory of Behavioral Genetics, Brain Mind Institute, Ecole Polytechnique Federale de Lausanne (EPFL), Lausanne, Switzerland Abstract The stimulation of adult hippocampal neurogenesis by antidepressants has been associated with multiple molecular pathways, but the potential influence exerted by other brain areas has received much less attention. The basolateral complex of the amygdala (BLA), a region involved in anxiety and a site of action of antidepressants, has been implicated in both basal and stress-induced changes in neural plasticity in the dentate gyrus. We investigated here whether the BLA modulates the effects of the SSRI antidepressant fluoxetine on hippocampal cell proliferation and survival in relation to a behavioral index of depression-like behavior (forced swim test). We used a lesion approach targeting the BLA along with a chronic treatment with fluoxetine, and monitored basal anxiety levels given the important role of this behavioral trait in the progress of depression. Chronic fluoxetine treatment had a positive effect on hippocampal cell survival only when the BLA was lesioned. Anxiety was related to hippocampal cell survival in opposite ways in sham- and BLA-lesioned animals (i.e., negatively in sham- and positively in BLA-lesioned animals). Both BLA lesions and low anxiety were critical factors to enable a negative relationship between cell proliferation and depressi