Carvalho-Netto E F, Nunes-de-Souza R L
Lab de Farmacologia da Faculdade de Ciências Farmacêuticas-Campus UNESP, Rod Araraquara-Jau, Km 01 Farmacologia, Araraquara, SP 14801-902, Brazil.
Behav Brain Res. 2004 Jan 5;148(1-2):119-32. doi: 10.1016/s0166-4328(03)00184-0.
We have recently suggested that the elevated T-maze (ETM) is not a useful test to study different types of anxiety in mice if a procedure similar to that originally validated for rats is employed. The present study investigated whether procedural (five exposures in the enclosed arm instead of three as originally described for rats) and structural (transparent walls instead of opaque walls) changes to the ETM leads to consistent inhibitory avoidance acquisition (IAA) and low escape latencies in mice. Results showed that five exposures to the ETM provoked consistent IAA, an effect that was independent of the ETM used. However, the ETM with transparent walls (ETMt) seemed to be more suitable for the study of conditioned anxiety (i.e. IAA) and unconditioned fear (escape) in mice, since IAA (low baseline latency with a gradual increase over subsequent exposures) and escape (low latency) profiles rendered it sensitive to the effects of anxiolytic and anxiogenic drugs. In addition to evaluation of drug effects on IAA and escape, the number of line crossings in the apparatus were used to control for locomotor changes. Results showed that whereas diazepam (1.0-2.0 mg/kg) and flumazenil (10-30 mg/kg) impaired IAA, FG 7142 (10-30 mg/kg) did not provoke any behavioral change. Significantly, none of these benzodiazepine (BDZ) receptor ligands modified escape latencies. The 5-HT1A partial receptor agonist buspirone (1.0-2.0 mg/kg) and the 5-HT releaser fenfluramine (0.15-0.30 mg/kg) impaired IAA and facilitated escape, while the full 5-HT1A receptor agonist, 8-OH-DPAT (0.05-0.1 mg/kg) and the 5-HT(2B/2C) receptor antagonist, SER 082 (0.5-2.0 mg/kg) failed to modify either response. mCPP (0.5-2.0 mg/kg), a 5-HT(2B/2C) receptor agonist, facilitated IAA but did not alter escape latency. Neither antidepressant utilized in the current study, imipramine (1.0-5.0 mg/kg) and moclobemide (3.0-10 mg/kg) affected IAA or escape performance in mice. The well-known anxiogenic drugs yohimbine (2.0-8.0 mg/kg) and caffeine (10-30 mg/kg) did not selectively affect IAA, although caffeine did impair escape latencies. Present results suggest the ETMt is useful for the study of conditioned anxiety in mice. However, upon proximal threats (e.g. open arm exposure), mice do not exhibit escape behavior as an immediate defensive strategy, suggesting that latency to leave open arm is not a useful parameter to evaluate unconditioned fear in this species.
我们最近提出，如果采用与最初针对大鼠验证的程序类似的方法，高架T迷宫（ETM）并非研究小鼠不同类型焦虑的有用测试。本研究调查了ETM的程序变化（在封闭臂中进行五次暴露，而非最初描述的大鼠的三次）和结构变化（透明壁而非不透明壁）是否会导致小鼠出现一致的抑制性回避习得（IAA）和低逃避潜伏期。结果显示，对ETM进行五次暴露可引发一致的IAA，这一效应与所使用的ETM无关。然而，具有透明壁的ETM（ETMt）似乎更适合用于研究小鼠的条件性焦虑（即IAA）和非条件性恐惧（逃避），因为IAA（低基线潜伏期且在后续暴露中逐渐增加）和逃避（低潜伏期）特征使其对抗焦虑和致焦虑药物的作用敏感。除了评估药物对IAA和逃避的影响外，还使用装置中的穿行次数来控制运动变化。结果显示，地西泮（1.0 - 2.0 mg/kg）和氟马西尼（10 - 30 mg/kg）损害IAA，而FG 7142（10 - 30 mg/kg）未引发任何行为变化。值得注意的是，这些苯二氮䓬（BDZ）受体配体均未改变逃避潜伏期。5 - HT1A部分受体激动剂丁螺环酮（1.0 - 2.0 mg/kg）和5 - HT释放剂芬氟拉明（0.15 - 0.30 mg/kg）损害IAA并促进逃避，而完全5 - HT1A受体激动剂8 - OH - DPAT（0.05 - 0.1 mg/kg）和5 - HT（2B/2C）受体拮抗剂SER 082（0.5 - 2.0 mg/kg）未能改变任何一种反应。mCPP（0.5 - 2.0 mg/kg），一种5 - HT（2B/2C）受体激动剂，促进IAA但未改变逃避潜伏期。本研究中使用的两种抗抑郁药，丙咪嗪（1.0 - 5.0 mg/kg）和吗氯贝胺（3.0 - 10 mg/kg）均未影响小鼠的IAA或逃避表现。著名的致焦虑药物育亨宾（2.0 - 8.0 mg/kg）和咖啡因（10 - 30 mg/kg）并未选择性地影响IAA，尽管咖啡因确实损害了逃避潜伏期。目前结果表明ETMt可用于研究小鼠的条件性焦虑。然而，在接近威胁时（如开放臂暴露），小鼠不会表现出逃避行为作为即时防御策略，这表明离开开放臂的潜伏期并非评估该物种非条件性恐惧的有用参数。
