Tonic immobility in guinea pigs: A behavioural response for detecting an anxiolytic-like effect?
Tonic immobility in guinea pigs: A behavioural response for detecting an anxiolytic-like effect?
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DOI：
10.1097/00008877-200207000-00002
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发表时间：
2002-07-01
影响因子：
1.6
通讯作者：
Lapiz, MDS
中科院分区：
文献类型：
--
作者：
Olsen, CK;Hogg, S;Lapiz, MDS
紧张性不动（TI）被认为是一种先天性的恐惧反应，其特征是暂时的深刻和可逆的运动抑制状态。TI发生在广泛的物种中的捕食者-猎物的对抗，并被假设为终端防御反应发生时，有猎物和捕食者之间的物理接触。本研究的目的是研究豚鼠TI模型用于检测抗焦虑和/或抗抑郁药物活性的有效性。降低TI的化合物包括5-羟色胺（5-HT）激动剂芬氟拉明、5-HT 1A受体激动剂8-羟基-2-羟色胺（8-HT）、（二正丙基氨基）四氢化萘（8-OH-DPAT）和丁螺环酮，5-HT 2C/2B受体拮抗剂SB 206553，5-HT 2A受体拮抗剂MDL 100.151 -但仅在认为也抑制5-HT 2C受体的剂量下-去甲肾上腺素（NA）再摄取抑制剂地昔帕明、苯并二氮杂反向激动剂FG-7142、α（2）-肾上腺素能受体拮抗剂育亨宾、神经激肽（NK）（1）受体拮抗剂L-733.060和NK 2受体拮抗剂SR-48968。增加TI的化合物包括苯二氮卓类激动剂地西泮和阿普唑仑，以及α（2）-肾上腺素能受体激动剂可乐定。选择性5-HT再摄取抑制剂西酞普兰、帕罗西汀和氟西汀、5-HT 1A受体拮抗剂WAY 100.635、5-HT 2C受体激动剂MK-212、5-HT/NA再摄取抑制剂丙咪嗪、NA再摄取抑制剂他洛普伦、苯二氮类拮抗剂氟马西尼、α 2-肾上腺素能受体拮抗剂咪唑克生和精神苯丙胺兴奋剂均无任何作用。这些结果表明，肾上腺素能，去甲肾上腺素能和神经激肽系统参与介导或调节豚鼠的TI行为。由于苯二氮卓类配体的矛盾作用，可能会质疑TI作为检测抗焦虑样作用的行为的潜力，这可能归因于化合物的镇静和/或共济失调作用。然而，有临床前证据表明5-HT 1A受体激动剂、5-HT 2C受体拮抗剂和NK 1和NK 2受体拮抗剂具有抗焦虑潜力。只有当非苯二氮卓类配体（例如NK受体拮抗剂）的抗焦虑潜力的临床研究结果可用时，才有可能完全确定TI模型的预测有效性。(C)2002年利平科特威廉姆斯威尔金斯。
Tonic immobility (TI) is considered to be an innate fear response characterized by a temporary state of profound and reversible motor inhibition. TI occurs in a wide range of species in a predator-prey confrontation and is hypothesized to be a terminal defence response occurring when there is physical contact between prey and predator. The objective of the present study was to investigate the validity of the TI model in guinea pigs for detection of anxiolytic and/or antidepressant drug activity. Compounds that reduced TI include the serotonin (5-HT) releaser fenfluramine, the 5-HT1A receptor agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and buspirone, the 5-HT2C/2B receptor antagonist SB206553, the 5-HT2A receptor antagonist MDL 100.151 - but only at doses thought also to inhibit 5-HT2C receptors-the noradrenaline (NA) reuptake inhibitor desipramine, the benzodiazepine inverse agonist FG-7142, the alpha(2)-adrenergic receptor antagonist yohimbine, the neurokinin (NK)(1) receptor antagonist L-733.060, and the NK2 receptor antagonist SR-48968. Compounds that increased TI include the benzodiazepine agonists diazepam and alprazolam, and the alpha(2)-adrenergic receptor agonist clonidine. The selective 5-HT reuptake inhibitors citalopram, paroxetine and fluoxetine, the 5-HT1A receptor antagonist WAY100.635, the 5-HT2C receptor agonist MK-212, the 5-HT/NA reuptake inhibitor imipramine, the NA reuptake inhibitor talopram, the benzodiazepine antagonist flumazenil, the alpha(2)-adrenergic receptor antagonist idazoxan and the psychostimulant amphetamine did not have any effect. These findings indicate that the serotonergic, noradrenergic and neurokinin systems are involved in mediating or modulating TI behaviour in guinea pigs. The potential of TI as a behaviour for detecting anxiolytic-like effect may be questioned due to the contradictory effect of the benzodiazepine ligands, which may be attributed to the sedative and/or ataxic effects of the compounds. Nevertheless, there is preclinical evidence suggesting that 5-HT1A receptor agonists, 5-HT2C receptor antagonists and NK1 and NK2 receptor antagonists possess anxiolytic potential. Only when results of clinical investigations of the anxiolytic potential of non-benzodiazepine ligands (for example the NK receptor antagonists) are available, will it be possible to determine fully the predictive validity of the TI model. (C) 2002 Lippincott Williams Wilkins.