Antidepressant fluoxetine (Flx) is the first therapeutic choice for the treatment of major depression (MD), however neuroanatomical spots of its action remain unclear. Immunohistochemical detection of c-Fos protein expression has been used for mapping activated neuronal circuits upon various stressors and drugs. We investigated the effect of 3 weeks of Flx treatment (15 mg/kg/day) on changes in neuronal activity, by mapping the number of c-Fos⁺ cells, in several brain subregions in adult male rats of control and following 3 weeks of chronic social isolation (CSIS), an animal model of depression. The aim was to identify brain subregions activated by vehicle or Flx treatment in both controls or simultaneously applied with CSIS. Flx prevented depressive- and anxiety-like behaviors in CSIS rats. In controls, Flx increased the number of c-Fos⁺ cells in the anterior/posterior piriform cortex (aPirCx, pPirCx), retrosplenial cortex dysgranular (RSD) and granular, c region (RSGc), dorsal hippocampal subregions (CA1d, CA2, CA3d, DGd), lateral habenula (LHB), paraventricular thalamic nucleus, posterior part (PVP) and lateral/basolateral complex of amygdala (LA/BL). CSIS-induced neuronal activation was observed in brain subregions implicated in mood and other mental disorders such as aPirCx, pPirCx, caudate putamen (CPu), acumbens nucleus shell (AcbSh), RSD, RSGc, DGd, PVP and LA/BL. Flx increased neuronal activation in both controls and CSIS rats in the CA1d, CA2, CA3d, PVP, LA/BL, while in striatum increased neuronal activation was observed only in CSIS. Our data identify activated CSIS-related brain subregions and/or Flx treatment, in which Flx increased c-Fos protein expression in CSIS rats.

抗抑郁药氟西汀 (Flx) 是治疗重度抑郁症 (MD) 的首选药物，但其作用的神经解剖学点仍不清楚。c-Fos 蛋白表达的免疫组织化学检测已被用于在各种压力源和药物上绘制激活的神经元回路。我们通过绘制 c-Fos ⁺细胞，在成年雄性大鼠的几个大脑亚区中，以及在慢性社会隔离 (CSIS) 3 周后，抑郁症动物模型。目的是确定在两个对照中或同时应用 CSIS 的载体或 Flx 治疗激活的大脑亚区。Flx 可防止 CSIS 大鼠出现抑郁和焦虑样行为。在对照中，Flx 增加了 c-Fos ⁺前/后梨状皮层 (aPirCx, pPirCx)、脾后皮质颗粒障碍 (RSD) 和颗粒、c 区 (RSGc)、海马背亚区 (CA1d、CA2、CA3d、DGd)、外侧缰核 (LHB)、室旁丘脑中的细胞核、后部 (PVP) 和杏仁核的外侧/基底外侧复合体 (LA/BL)。在涉及情绪和其他精神障碍的大脑亚区中观察到 CSIS 诱导的神经元激活，例如 aPirCx、pPirCx、尾壳核 (CPu)、伏隔核壳 (AcbSh)、RSD、RSGc、DGd、PVP 和 LA/BL。Flx 增加了 CA1d、CA2、CA3d、PVP、LA/BL 中对照和 CSIS 大鼠的神经元激活，而在纹状体中仅在 CSIS 中观察到神经元激活增加。我们的数据确定了激活的 CSIS 相关大脑亚区和/或 Flx 治疗，