Regulation of stress-provoked aggressive behavior using endocannabinoids.
Regulation of stress-provoked aggressive behavior using endocannabinoids.
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DOI：
10.1016/j.ynstr.2021.100337
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发表时间：
2021-11
影响因子：
5
通讯作者：
Gean PW
中科院分区：
文献类型：
--
作者：
Chang CH;Liu YC;Sun CY;Su CL;Gean PW
反应性冲动攻击的特征是当受试者遇到威胁压力事件时，会爆发愤怒和暴力。虽然冲动攻击和暴力给健康和社会造成了高昂的负担，但人们对治疗方法知之甚少。青少年早期社会孤立（SI）会改变大脑发育和功能。在小鼠模型中，它诱导腹侧海马体（vHip）的过度兴奋，以促进急性应激引起的攻击爆发，即冲动性攻击。大麻素1型受体（CB1Rs）作用于突触前位点并抑制神经递质释放到突触。鉴于CB1R激活抑制神经递质释放并调节兴奋性网络活动，我们验证了CB1R激活通过降低vHip中的兴奋性活动来减少SI小鼠冲动攻击的假设。在这里，我们报告了CB1R激动剂WIN-552122 （WIN）或花生四烯基环丙酰胺（ACPA），在不影响一般运动活动的情况下改善了居住入侵者测试中的急性应激性攻击行为。通过抑制vHip中的降解酶来增加内源性大麻素（eCBs），可以减少冲动攻击，而给药AM251（一种CB1R拮抗剂）可以减弱这种作用。急性应激在SI小鼠中诱导c-Fos表达，这是神经元激活的标志，在vHip神经元上投射到下丘脑腹内侧（VMH），这是一个众所周知的控制攻击行为的大脑区域。eCB增强抑制CB1Rs包围的vmh -突起vHip神经元中c-Fos的表达。这些结果表明，增强eCB信号以激活CB1Rs通过抑制vHip→VMH神经活动来抑制冲动性攻击，并指出CB1R激活在改善青春期早期有不良经历的成年人的冲动性攻击中的作用。青少年早期社会孤立促进冲动性攻击。CB1R激动剂治疗可减少SI小鼠的冲动性攻击。增加内源性大麻素（eCBs）以激活CB1Rs可减少冲动攻击。增强的eCBs抑制了海马体中应激引起的神经元激活。
Reactive impulsive aggression is characterized by outbursts of rage and violence when subjects encounter threatening stressful events. Although impulsive aggression and violence create a high-cost burden on health and society, relatively little is known about treatment. Early adolescent social isolation (SI) alters brain development and functions. It induces hyper-excitatory in the ventral hippocampus (vHip) to promote acute stress-provoked outbursts of aggression, referred to as impulsive aggression, in mouse models. Cannabinoid type 1 receptors (CB1Rs) act on presynaptic sites and suppress neurotransmitter release into synapses. Given that CB1R activation inhibits neurotransmitter releases and modulates excitatory network activity, we tested the hypothesis that CB1R activation reduces impulsive aggression in SI mice through decreasing excitatory activity in the vHip. Here, we report that CB1R agonists, WIN-552122 (WIN) or arachidonylcyclopropylamide (ACPA), ameliorated acute stress-provoked attack behavior in the resident-intruder test without affecting general locomotion activity. Increasing endocannabinoids (eCBs) by inhibiting degradation enzymes in the vHip reduced impulsive aggression, and the effect was blunted by administration of AM251, a CB1R antagonist. Acute stress in SI mice induced c-Fos expression, a marker of neuronal activation, on vHip neurons projecting to the ventromedial hypothalamus (VMH), a well-known brain area that controls attack behavior. eCB augmentation inhibited c-Fos expression in VMH-projecting vHip neurons surrounded by CB1Rs. These results suggest that enhancing eCB signaling in order to activate CB1Rs suppresses impulsive aggression via suppressing vHip→VMH neural activity and point to a role of CB1R activation in ameliorating impulsive aggression in adults who have had adverse experiences during early adolescence. Early adolescent social isolation (SI) promotes impulsive aggression. Treatment of CB1R agonists reduces impulsive aggression in SI mice. Increasing endocannabinoids (eCBs) to activate CB1Rs reduces impulsive aggression. Augmenting eCBs suppresses stress-provoked neuronal activation in the hippocampus.
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影响因子：
4.7
作者：
Araque A;Castillo PE;Manzoni OJ;Tonini R
通讯作者：
Tonini R
影响因子：
16.2
作者：
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通讯作者：
Patel S
影响因子：
3.5
作者：
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通讯作者：
Gean, Po-Wu