Department of Biology, Valdosta State University, Valdosta, GA 31698, USA.
Behav Brain Res. 2011 Mar 17;218(1):8-14. doi: 10.1016/j.bbr.2010.11.029. Epub 2010 Nov 20.
Clinical evidence in humans suggests that there is some linkage between dysfunction in the timing of circadian rhythms and certain types of depression. In animal models, Syrian hamsters have been used extensively to study the pharmacology of circadian rhythms, while rats and mice are used to screen putative anxiolytics/antidepressant compounds. It would be beneficial to be able to test anxiolytic/antidepressant compounds in hamsters in conjunction with circadian rhythm studies. Therefore, in this study, Syrian hamsters were used in three experimental paradigms to evaluate anxiety: the elevated plus maze, the t-tube, and the open field Thatcher-Britton conflict test. Diazepam, tested with 2mg/kg and 5mg/kg intraperitoneal injections, was found to induce anxiolytic activity in each of the three tests. Hamsters were more likely to spend time in the open arms in the plus maze, displayed more exploratory behavior in the t-tube, and were quicker to enter a brightly lit exposed field in the Thatcher-Britton conflict test following injections of diazepam. Diazepam (2mg/kg) was also tested at three times during the 24-h day in the elevated plus maze: at the beginning and end of the lights-on period (Zeitgeber times 23 and 11, respectively) and once in the dark just before the room lights came on (Zeitgeber time 20). Diazepam induced anxiolytic activity only at Zeitgeber 23. Therefore, the following known and putative anxiolytic compounds were also evaluated in each of the three tests at Zeitgeber 23: citalopram, the neurokinin(1) receptor antagonists GR205171 and vestipitant, the corticotropin releasing factor(1) receptor antagonist CP154526, the cannabinoid receptor(1) agonist CP55940, the serotonin(6) receptor antagonist SB399885, and the metabotropic glutamate receptor(5) antagonists fenobam and MTEP. Vestipitant displayed some anxiolytic activity in the elevated plus maze, but this effect was not confirmed with GR205171. None of the other compounds displayed any anxiolytic activity in the tests. Nevertheless, the present results with diazepam - together with a few reports from other laboratories, indicate that the elevated plus maze may be a suitable procedure for evaluating the actions of anxiolytic compounds in Syrian hamsters. In view of current interest in novel classes of psychotropic agent interacting with diverse GABA(A) receptor recognition sites, further characterization appears justified.
临床证据表明，人体昼夜节律功能障碍与某些类型的抑郁症之间存在一定联系。在动物模型中，叙利亚仓鼠被广泛用于研究昼夜节律的药理学，而大鼠和小鼠则用于筛选潜在的抗焦虑/抗抑郁化合物。如果能够在研究昼夜节律的同时在仓鼠身上测试抗焦虑/抗抑郁化合物，将会非常有益。因此，在这项研究中，叙利亚仓鼠被用于三种实验范式来评估焦虑：高架十字迷宫、t 型管和开阔场 Thatcher-Britton 冲突测试。地西泮以 2mg/kg 和 5mg/kg 腹腔注射进行测试，结果发现它在三种测试中均表现出抗焦虑活性。注射地西泮后，仓鼠更有可能在高架十字迷宫的开放臂中花费时间，在 t 型管中表现出更多的探索行为，并且在 Thatcher-Britton 冲突测试中更快地进入明亮暴露的野外。地西泮（2mg/kg）还在 24 小时内的高架十字迷宫中的三个时间点进行了测试：在光照期的开始和结束时（分别为 Zeitgeber 时间 23 和 11），以及在房间灯光亮起前的黑暗中一次（Zeitgeber 时间 20）。地西泮仅在 Zeitgeber 23 时诱导抗焦虑活性。因此，以下已知和潜在的抗焦虑化合物也在 Zeitgeber 23 时在三种测试中的每一种中进行了评估：西酞普兰、神经激肽(1)受体拮抗剂 GR205171 和 vestipitant、促肾上腺皮质释放因子(1)受体拮抗剂 CP154526、大麻素受体(1)激动剂 CP55940、血清素(6)受体拮抗剂 SB399885 和代谢型谷氨酸受体(5)拮抗剂 fenobam 和 MTEP。Vestipitant 在高架十字迷宫中显示出一些抗焦虑活性，但这一效果并未在 GR205171 中得到证实。其他化合物在测试中均未显示出任何抗焦虑活性。尽管如此，目前地西泮的结果——以及其他几个实验室的一些报告——表明高架十字迷宫可能是评估叙利亚仓鼠中抗焦虑化合物作用的合适程序。鉴于目前对与不同 GABA(A) 受体识别位点相互作用的新型精神药物类别的兴趣，进一步的特征描述似乎是合理的。
