Antidepressant-like responses to lithium in genetically diverse mouse strains.
Antidepressant-like responses to lithium in genetically diverse mouse strains.
复制标题
DOI：
10.1111/j.1601-183x.2011.00682.x
复制
发表时间：
2011-06
期刊：
影响因子：
--
通讯作者：
Gould TD
中科院分区：
文献类型：
--
作者：
Can A;Blackwell RA;Piantadosi SC;Dao DT;O'Donnell KC;Gould TD
仅在双相情感障碍和抑郁症患者的亚组中发现锂具有稳定情绪和抗抑郁的作用。鉴定对锂有反应和无反应的小鼠品系可以阐明在锂反应中发挥作用的基因组和其他生物因素。在急性和慢性全身、脑室内和慢性锂治疗后，对小鼠品系进行强迫游泳、尾悬吊和旷场测试。测量血清和脑锂水平。所测试的八个近交菌株中的三个（129S6/SvEvTac、C3H/HeNHsd、C57BL/6J）和三个远交菌株中的一个（CD-1）在急性全身锂给药后的强迫游泳测试中显示出抗抑郁样反应。三种有反应的近交系以及 DBA/2J 品系在长期施用锂后的强迫游泳测试中也有反应。然而，在悬尾试验中，急性锂仅在 C3H/HeNHsd 小鼠中产生抗抑郁样作用。在长期给予锂后，只有 C57BL/6J 和 DBA/2J 在尾部悬挂试验中有反应。脑室内锂给药在 BALB/cJ（无反应）和 C57BL/6J（反应）菌株中产生相似的反应特征。血清和脑内锂浓度表明，行为结果并非由于个体菌株中锂的药代动力学差异所致，这表明遗传因素可能调节对锂的反应。我们的结果表明，在抗抑郁功效测试中，不同遗传多样性小鼠品系对锂的反应各不相同。这些结果将有助于确定与锂反应性和锂作用机制相关的基因组因素。
A mood stabilizing and antidepressant response to lithium is only found in a subgroup of bipolar disorder and depression patients. Identifying strains of mice that are responsive and non-responsive to lithium may elucidate genomic and other biological factors that play a role in lithium responsiveness. Mouse strains were tested in the forced swim, tail suspension, and open field tests after acute and chronic systemic, and intracerebroventricular and chronic lithium treatments. Serum and brain lithium levels were measured. Three (129S6/SvEvTac, C3H/HeNHsd, C57BL/6J) of the eight inbred strains tested, and one (CD-1) of the three outbred strains, showed an antidepressant-like response in the forced swim test following acute systemic administration of lithium. The three responsive inbred strains, as well as the DBA/2J strain, were also responsive in the forced swim test after chronic administration of lithium. However, in the tail suspension test, acute lithium resulted in an antidepressant-like effect only in C3H/HeNHsd mice. Only C57BL/6J and DBA/2J were responsive in the tail suspension test after chronic administration of lithium. Intracerebroventricular lithium administration resulted in a similar response profile in BALB/cJ (non-responsive) and C57BL/6J (responsive) strains. Serum and brain lithium concentrations demonstrated that behavioral results were not due to differential pharmacokinetics of lithium in individual strains, suggesting that genetic factors likely regulate responsiveness to lithium. Our results indicate that responsiveness to lithium in tests of antidepressant efficacy varies among genetically diverse mouse strains. These results will assist in identifying genomic factors associated with lithium responsiveness and the mechanisms of lithium action.