Ethopharmacology of imipramine in the forced-swimming test: gender differences
Ethopharmacology of imipramine in the forced-swimming test: gender differences
复制标题
DOI：
10.1016/s0149-7634(98)00029-3
复制
发表时间：
1998-12-01
影响因子：
8.2
通讯作者：
Ferigolo, M
中科院分区：
文献类型：
--
作者：
Barros, HMT;Ferigolo, M
大多数用于测定预期新药剂功效的临床前试验是用雄性实验动物进行的。在这种情况下，很大一部分人口被忽视，因为新药剂的作用与女性荷尔蒙波动的相互作用也被忽视。本研究综述了强迫游泳试验的技术程序特点和测试程序诱导的行为结果在男性。它还使用详细的行为评分比较了经典抗抑郁药丙咪嗪（IMI）在雄性和雌性大鼠中的抗不动作用。在行为测试开始前对雌性大鼠进行阴道涂片，并在重新测试前24 h、5 h和1 h给予三种剂量，雄性大鼠也是如此。实验采用录像法，分析强迫游泳过程中行为的频率和持续时间。在重新测试期间，雄性大鼠大约有50%的时间不动。有一个显着的，剂量依赖性的减少不动持续时间和减少头部晃动的雄性大鼠与IMI。三环类抗抑郁药同样增强了攀爬和游泳的主动行为，攀爬行为占移动的行为的75%。在强迫游泳过程中，雌性动物的不动时间和摇头频率明显低于雄性动物，而移动的行为持续时间则长于雄性动物。丙咪嗪只降低雌性的不动频率和摇头次数，增加爬池的逃避行为，减少在池中游泳。这种作用在发情期和发情前期更为明显。这些结果表明，在强迫游泳测试中，男性和女性之间的主要行为差异。它还阐明了丙咪嗪的影响是可测量的男性使用的行为的持续时间，而行为的频率修改与丙咪嗪治疗的女性。(C)1998爱思唯尔科技有限公司版权所有。
Most of the pre-clinical tests used to assay the efficacy of prospective new agents are done with male experimental animals. In this case, a large part of the population is disregarded as is the interaction of the new agent's effects with female hormonal fluctuations. The present study reviews the technical procedures characteristic for the forced-swimming test and the behavioral outcome induced by the testing procedure in males. It also compares the anti-immobility effects of the classic antidepressant imipramine (IMI) in male and female rats using a detailed behavioral scoring. Female rats had vaginal smears done before the beginning of the behavioral testing and were administered with three doses 24 h, 5 h and 1 h before the retest, as were male rats. Tests were videotape-recorded for analysis of the frequency and duration of the behaviors during forced-swimming. Male rats spend around 50% of the time immobile during the retest. There was a significant, dose dependent decrease in immobility duration and a decrease in head-shakes of male rats treated with IMI. Both active behaviors of climbing and swimming were equally enhanced by the tricyclic antidepressant, climbing behavior comprising 75% of the mobile behaviors. Females showed much lower immobility duration and head-shake frequency during the forced-swimming than males and spent longer periods in mobile behaviors. Imipramine only decreases immobility frequency and head-shakes of females, and increases the escape-type behavior of climbing, decreasing swimming in the middle of the tank. This effect is more noticeable during estrus and proestrus. These results demonstrate the main behavioral differences between males and females in the forced-swimming test. It also elucidates that the effects of imipramine are measurable in males using the duration of the behaviors, while the frequencies of behaviors are modified in females treated with imipramine. (C) 1998 Elsevier Science Ltd. All rights reserved.