Sensitivity to the effects of pharmacologically selective antidepressants in different strains of mice
Sensitivity to the effects of pharmacologically selective antidepressants in different strains of mice
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DOI：
10.1007/s002130100694
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发表时间：
2001-05-01
影响因子：
3.4
通讯作者：
Mayorga, AJ
中科院分区：
文献类型：
--
作者：
Lucki, I;Dalvi, A;Mayorga, AJ
理论基础：神经行为遗传学的最新进展增加了对不同品系小鼠行为模式研究的重要性。对近交系和近交系小鼠进行了全面的比较，以提供有关强迫游泳试验的表现和药理作用的信息。强迫游泳试验是一种行为测试，通常用于衡量抗抑郁药物的效果。目的：在强迫游泳实验中，比较7个近交系和4个近交系小鼠对去甲肾上腺素再摄取抑制剂地昔帕明和5-羟色胺再摄取抑制剂氟西汀的基线表现和药理学反应。方法：将小鼠分别置于装满水的玻璃瓶中6min，进行游泳训练。测试最后4分钟内的行为不动持续时间由录像带评分。结果：固定值和变异系数的10倍范围支持小鼠品系之间在FST的基线表现上存在实质性的行为差异。总的来说，自交系的变异性比近交系的低。在测试的11个品系中，有7个品系的地塞帕明呈剂量依赖性地减少不动，DBA/2J和C57BL/6J小鼠比其他品系表现出更高的敏感性。相比之下，氟西汀只减少了11个品系中的3个，即DBA/2J，BALB/CJ和NIH瑞士小鼠的不动。结论：在小鼠FST中，背景菌株是决定基线表现和对不同类型抗抑郁药物敏感性的关键变量。使用这样的小鼠品系可能提供关于品系抑郁行为差异和对不同类别抗抑郁药物的不同敏感性的遗传基础的信息。
Rationale: Recent advances in neurobehavioral genetics have increased the importance of research on the behavioral patterns of different mouse strains. A comprehensive comparison of inbred and outbred mouse strains was conducted to provide information on the range of performance and pharmacological effects in the forced swimming test, a behavioral test commonly used to measure the effects of antidepressant drugs. Objectives: Baseline performance and pharmacological responses to desipramine, a selective norepinephrine reuptake inhibitor, and fluoxetine, a selective serotonin reuptake inhibitor, were compared in seven inbred and four outbred mouse strains in the forced swimming test. Methods: Swim sessions were conducted by placing mice in individual glass cylinders filled with water for 6 min. The duration of behavioral immobility during the last 4 min of the test was scored from videotapes. Results: A 10-fold range of immobility values and coefficient of variation supported the existence of substantial behavioral differences between mouse strains in baseline performance in the FST. In general, inbred strains demonstrated lower variability than outbred strains. Desipramine dose-dependently reduced immobility in seven of the 11 strains tested, with DBA/2J and the C57BL/6J mice showing greater sensitivity than the other strains. In contrast, fluoxetine reduced immobility in only three out of the 11 strains tested, DBA/2J, BALB/cJ and NIH Swiss mice. Conclusions: Background strain is a critical variable in determining baseline performance and the sensitivity to different types of antidepressant drugs in the mouse FST. The use of such mouse strains may provide information on the genetic basis for strain differences in depressive behavior and differential sensitivity to diverse classes of antidepressants.