Fluoxetine treatment induces dose dependent alterations in depression associated behavior and neural plasticity in female mice.
Fluoxetine treatment induces dose dependent alterations in depression associated behavior and neural plasticity in female mice.
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DOI：
10.1016/j.neulet.2010.07.084
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发表时间：
2010-10-22
影响因子：
2.5
通讯作者：
Lucki I
中科院分区：
文献类型：
--
作者：
Hodes GE;Hill-Smith TE;Lucki I
抗抑郁药诱导的啮齿类和灵长类动物神经发生和神经营养因子动员的增加被认为是行为功效所必需的。目前的研究探讨氟西汀治疗对女性行为、细胞增殖和神经营养因子BDNF的影响之间的关系。雌性MRL/MpJ小鼠急性（5和10 mg/kg）或慢性（2.5、5和10 mg/kg b.i.d.）分别进行悬尾试验（TST）和（或）新奇事物诱发的摄食减少试验（NIH）。长期接受氟西汀治疗的小鼠在治疗的最后4天接受4次（100 mg/kg）5-溴-2 ′-脱氧尿苷（BrdU）注射，以测量DNA合成。另一半海马和额叶皮质被移除，并检查BDNF水平。氟西汀治疗降低了TST中的不动性和NIH测试中的进食潜伏期，但只有最高剂量的氟西汀显著改变了两项测试中的行为。5和10 mg/kg氟西汀的慢性治疗显著增加了海马中的细胞增殖和BDNF水平。只有最高剂量氟西汀的慢性治疗增加了额叶皮层的BDNF水平。NIH测试中的行为测量与额叶皮质中的BDNF水平相关，但与海马中的BDNF水平或海马中的细胞增殖无关。这些数据表明，女性需要高剂量的氟西汀的行为疗效，无论海马神经发生和BDNF动员的海拔。额叶皮质中BDNF水平的升高与氟西汀的行为疗效有关。
Antidepressant induced increases in neurogenesis and neurotrophin mobilization in rodents and primates are proposed to be necessary for behavioral efficacy. The current study examines the relationship between the effects of fluoxetine treatment on behavior, cell proliferation and the neurotrophin BDNF in females. Female MRL/MpJ mice were treated acutely (5 and 10 mg/kg) or chronically (2.5, 5 and 10 mg/kg b.i.d.) with fluoxetine and tested in the tail suspension test (TST) and or novelty induced hypophagia test (NIH) respectively. Mice treated chronically with fluoxetine received 4 (100 mg/kg) injections of 5-bromo-2′-deoxyuridine (BrdU) on the last 4 days of treatment to measure DNA synthesis. The other half of the hippocampus and the frontal cortex were removed and examined for BDNF levels. Fluoxetine treatment decreased immobility in the TST and latency to eat in the NIH test, but only the highest dose of fluoxetine significantly altered behavior in both tests. Chronic treatment with 5 and 10 mg/kg of fluoxetine significantly increased cell proliferation and BDNF levels in the hippocampus. Only chronic treatment with the highest of fluoxetine increased BDNF levels in the frontal cortex. Behavioral measures in the NIH test correlated with BDNF levels in the frontal cortex but not in the hippocampus or with cell proliferation in the hippocampus. These data suggest that females require high doses of fluoxetine for behavioral efficacy regardless of elevations of neurogenesis and BDNF mobilization in the hippocampus. Elevations in BDNF levels in the frontal cortex are related to the behavioral efficacy of fluoxetine.