Characterization of the profile of neurokinin-2 and neurotensin receptor antagonists in the mouse defense test battery
Characterization of the profile of neurokinin-2 and neurotensin receptor antagonists in the mouse defense test battery
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DOI：
10.1016/s0149-7634(01)00045-8
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发表时间：
2001-12-01
影响因子：
8.2
通讯作者：
Soubrié, P
中科院分区：
文献类型：
--
作者：
Griebel, G;Moindrot, N;Soubrié, P
低等哺乳动物面临掠夺性刺激时的防御行为为研究与人类情绪障碍相关的行为提供了适当的实验室模型。鼠标防御测试组（MDTB）的开发是因为它结合了防御的许多方面。简而言之，它由五项测试组成，这些测试要么与潜在威胁（情境防御）相关，要么与正在逼近的威胁（老鼠）的实际存在相关。后者侧重于飞行、风险评估以及防御威胁和攻击行为的变化。对抗焦虑化合物的研究表明，这些防御反应可用于区分几类抗焦虑药物。在这里，我们使用 MDTB 比较了苯二氮卓类地西泮与神经肽受体拮抗剂的行为特征，神经肽受体拮抗剂已被证明参与应激反应的调节，即 NK2 受体拮抗剂 SR48968 (0.01-1 mg/kg) 和 SR144190 (1-10 mg/kg) 以及 NT1 受体拮抗剂 SR48692 (1-30 mg/kg)。结果显示，所有化合物均降低了防御威胁/攻击，但只有地西泮和 SR48692 显着改变了风险评估或逃跑（程度较小）。此外，没有一种神经肽受体拮抗剂能够改变背景防御。总体而言，地西泮和 MDTB 中后面这些化合物所表现出的行为特征与抗焦虑样作用一致。然而，我们的结果表明，虽然 NK2 和 NT1 受体拮抗剂对焦虑相关反应（包括认知方面（即风险评估））的功效可能有限，但它们可能具有对抗某些形式的焦虑症的潜力，这些焦虑症涉及对极端压力刺激的适应性反应（例如直接对抗威胁刺激）。 (C) 2002 Elsevier Science Ltd. 保留所有权利。
Defensive behaviors of lower mammals confronted with a predatory stimulus provide an appropriate laboratory model for investigating behavior relevant to human emotional disorders. The mouse defense test battery (MDTB) has been developed because it combines many of the aspects of defense. Briefly, it consists of five tests either associated with potential threat (contextual defense) or the actual presence of an approaching threat (a rat). These latter focus on changes in flight, risk assessment and defensive threat and attack behaviors. Investigations with anxiolytic compounds have shown that these defense reactions may be used to differentiate between several classes of anxiolytic drugs. Here we used the MDTB to compare the behavioral profile of the benzodiazepine diazepam with that of neuropeptide receptor antagonists which have been shown to be involved in the modulation of stress response, namely the NK2 receptor antagonists, SR48968 (0.01-1 mg/kg) and SR144190 (1-10 mg/kg), and the NT1 receptor antagonist, SR48692 (1-30 mg/kg). Results showed that all compounds decreased defensive threat/attack, but only diazepam and, to a lesser extent, SR48692 significantly modified risk assessment or flight. Further, none of the neuropeptide receptor antagonists modified contextual defense. Overall, the behavioral profile displayed by diazepam and these latter compounds in the MDTB are consistent with an anxiolytic-like action. However, our results suggest that, while NK2 and NT1 receptor antagonists may have limited efficacy on anxiety-related responses including cognitive aspects (i.e. risk assessment), they may have a potential against some forms of anxiety disorders which involve adaptative responses to extreme stress stimuli (e.g. direct confrontation with the threat stimulus). (C) 2002 Elsevier Science Ltd. All rights reserved.