Varty Geoffrey B, Morgan Cynthia A, Cohen-Williams Mary E, Coffin Vicki L, Carey Galen J
CNS Biological Research, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
Neuropsychopharmacology. 2002 Sep;27(3):357-70. doi: 10.1016/S0893-133X(02)00312-3.
Several neurokinin NK1 receptor antagonists currently being developed for anxiety and depression have reduced affinity for the rat and mouse NK1 receptor compared with human. Consequently, it has proven difficult to test these agents in traditional rat and mouse models of anxiety and depression. This issue has been overcome, in part, by using non-traditional lab species such as the guinea pig and gerbil, which have NK1 receptors closer in homology to human NK1 receptors. However, there are very few reports describing the behavior of gerbils in traditional models of anxiety. The aim of the present study was to determine if the elevated plus-maze, a commonly used anxiety model, could be adapted for the gerbil. Using a specially-designed elevated plus-maze, gerbils exhibited an 'anxious' behavioral profile similar to that observed in rats and mice, i.e., reduced entries into, and time spent exploring, an open, aversive arm. The anxiolytic drugs diazepam (0.03-3 mg/kg i.p.), chlordiazepoxide (0.3-10 mg/kg i.p.), and buspirone (0.3-30 mg/kg s.c.) increased open arm exploration and produced anxiolytic-like effects on risk-assessment behaviors (reduced stretch-attend postures and increased head dips). Of particular interest, the antidepressant drugs imipramine (1-30 mg/kg p.o.), fluoxetine (1-30 mg/kg, p.o.) and paroxetine (0.3-10 mg/kg p.o.) each produced some acute anxiolytic-like activity, without affecting locomotor activity. The antipsychotic, haloperidol, and the psychostimulant, amphetamine, did not produce any anxiolytic-like effects (1-10 mg/kg s.c). The anxiogenic beta-carboline, FG-7142, reduced time spent in the open arm and head dips, and increased stretch-attend postures (1-30 mg/kg, i.p.). These studies have demonstrated that gerbils exhibit an anxiety-like profile on an elevated plus-maze, and that the gerbil elevated plus-maze may have predictive validity for anxiolytics, and antidepressants with potential anxiolytic-like effects.
目前正在研发的几种用于治疗焦虑和抑郁的神经激肽NK1受体拮抗剂，与人类相比，对大鼠和小鼠NK1受体的亲和力降低。因此，在传统的大鼠和小鼠焦虑与抑郁模型中测试这些药物已被证明具有难度。通过使用非传统实验物种，如豚鼠和沙鼠，部分解决了这个问题，这些物种的NK1受体与人类NK1受体的同源性更高。然而，很少有报告描述沙鼠在传统焦虑模型中的行为表现。本研究的目的是确定常用的焦虑模型——高架十字迷宫是否适用于沙鼠。使用专门设计的高架十字迷宫，沙鼠表现出与大鼠和小鼠类似的“焦虑”行为特征，即进入开放、厌恶臂的次数减少，在该臂探索的时间缩短。抗焦虑药物地西泮（腹腔注射0.03 - 3mg/kg）、氯氮卓（腹腔注射0.3 - 10mg/kg）和丁螺环酮（皮下注射0.3 - 30mg/kg）增加了在开放臂的探索，并对风险评估行为产生抗焦虑样作用（减少伸展-关注姿势，增加头部下垂）。特别值得关注的是，抗抑郁药物丙咪嗪（口服1 - 30mg/kg）、氟西汀（口服1 - 30mg/kg）和帕罗西汀（口服0.3 - 10mg/kg）各自都产生了一些急性抗焦虑样活性，且不影响运动活性。抗精神病药物氟哌啶醇和精神兴奋剂苯丙胺（皮下注射1 - 10mg/kg）未产生任何抗焦虑样作用。致焦虑的β-咔啉FG - 7142减少了在开放臂的停留时间和头部下垂次数，并增加了伸展-关注姿势（腹腔注射1 - 30mg/kg）。这些研究表明，沙鼠在高架十字迷宫上表现出类似焦虑的特征，并且沙鼠高架十字迷宫可能对抗焦虑药以及具有潜在抗焦虑样作用的抗抑郁药具有预测效度。
