Department of Stress Neurobiology, Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, 80804, Munich, Germany; Neuroscience Master's Program, Interdisciplinary Center for Neurosciences (IZN), Heidelberg University, Im Neuenheimer Feld 504, 69120, Heidelberg, Germany.
Department of Stress Neurobiology, Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, 80804, Munich, Germany.
Neuropharmacology. 2017 Nov;126:233-241. doi: 10.1016/j.neuropharm.2017.09.010. Epub 2017 Sep 7.
Our current knowledge of the implications of endocannabinoids in fear and anxiety is largely based on fear conditioning paradigms and approach-avoidance conflicts. Here we establish the ethobehavioral beetle mania task (BMT), which confronts mice with an erratically moving robo-beetle. With the help of this task we demonstrate decreased tolerance yet increased avoidance responses to an approaching beetle in high-anxiety behavior (HAB) and BALBc mice compared to C57BL/6N, CD1 and normal-anxiety behavior (NAB) mice. Also DBA/2N mice showed decreased passive and increased active behavior, but followed the robo-beetle more often than HAB and BALBc mice. Treatment with diazepam (1 mg/kg) increased tolerance without affecting avoidance behavior in HAB mice. Treatment with the MAGL inhibitor JZL184 (8 mg/kg) increased flight behavior, but did not affect tolerance. The FAAH inhibitor URB597 (0.3 mg/kg), however, reduced flight behavior and enhanced tolerance to the robo-beetle. The latter effects were blocked by co-treatment with the CB1 receptor antagonist SR141716A (3 mg/kg), which failed to affect the behavior by itself. Taken together, we validate the BMT as a novel test for studying endocannabinoids beyond traditional paradigms and for assessing active fear responses in mice. Furthermore, we demonstrate panicolytic consequences of pharmacological enhancement of anandamide, but not 2-AG signaling.
我们目前对内源性大麻素在恐惧和焦虑中的作用的了解在很大程度上基于恐惧条件反射范式和趋近-回避冲突。在这里，我们建立了行为学甲虫狂热任务（BMT），该任务使老鼠面对一只移动不稳定的机器甲虫。借助这个任务，我们证明了在高焦虑行为（HAB）和 BALBc 小鼠中，与 C57BL/6N、CD1 和正常焦虑行为（NAB）小鼠相比，对接近的甲虫的耐受性降低，但回避反应增加。DBA/2N 小鼠也表现出被动行为减少和主动行为增加，但比 HAB 和 BALBc 小鼠更经常跟随机器甲虫。地西泮（1mg/kg）治疗增加了 HAB 小鼠的耐受性而不影响回避行为。MAGL 抑制剂 JZL184（8mg/kg）治疗增加了飞行行为，但不影响耐受性。然而，FAAH 抑制剂 URB597（0.3mg/kg）减少了飞行行为并增强了对机器甲虫的耐受性。后一种作用被 CB1 受体拮抗剂 SR141716A（3mg/kg）的共同治疗阻断，而单独使用 SR141716A 则不会影响行为。总的来说，我们验证了 BMT 作为一种研究内源性大麻素的新方法，超越了传统的范式，并用于评估小鼠的主动恐惧反应。此外，我们证明了药理学增强花生四烯酸酰胺而不是 2-AG 信号传递的抗惊恐作用。
