Enhanced anandamide signaling reduces flight behavior elicited by an approaching robo-beetle
Enhanced anandamide signaling reduces flight behavior elicited by an approaching robo-beetle
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DOI：
10.1016/j.neuropharm.2017.09.010
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发表时间：
2017-11-01
影响因子：
4.7
通讯作者：
Wotjak, Carsten T.
中科院分区：
文献类型：
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作者：
Heinz, Daniel E.;Genewsky, Andreas;Wotjak, Carsten T.
我们目前对内源性大麻素在恐惧和焦虑中的影响的认识主要基于恐惧条件反射范式和接近-回避冲突。在这里，我们建立了行为甲虫躁狂症任务（BMT），该任务让小鼠面对一只不规则移动的机器甲虫。在这项任务的帮助下，我们证明了与C57 BL/6 N，CD 1和正常焦虑行为（NAB）小鼠相比，高焦虑行为（HAB）和BALBc小鼠对接近甲虫的耐受性降低，但回避反应增加。此外，DBA/2N小鼠表现出减少的被动行为和增加的主动行为，但比HAB和BALBc小鼠更经常地跟随机器甲虫。地西泮（1 mg/kg）治疗增加了耐受性，而不影响HAB小鼠的回避行为。用MAGL抑制剂JZL 184（8 mg/kg）处理增加了飞行行为，但不影响耐受性。然而，FAAH抑制剂URB 597（0.3 mg/kg）降低了飞行行为并增强了对机器甲虫的耐受性。后者的影响被CB 1受体拮抗剂SR 141716 A（3 mg/kg）联合给药阻断，其本身未能影响行为。总之，我们验证了BMT作为一种新的测试研究内源性大麻素超越传统的范式和评估小鼠的主动恐惧反应。此外，我们证明panicolytic后果的药理学增强花生四烯酸，但不是2-AG信号。(C)2017爱思唯尔有限公司版权所有
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. (C) 2017 Elsevier Ltd. All rights reserved.