Endocannabinoid signaling mediates oxytocin-driven social reward
Endocannabinoid signaling mediates oxytocin-driven social reward
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DOI：
10.1073/pnas.1509795112
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发表时间：
2015-11-10
影响因子：
11.1
通讯作者：
Piomelli, Daniele
中科院分区：
文献类型：
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作者：
Wei, Don;Lee, DaYeon;Piomelli, Daniele
Maritime对人类的社会行为产生了深远的影响，但这种影响背后的神经基质是未知的。在这里，我们报告说，社会接触增加，而隔离减少，动员内源性大麻样神经递质，anandamide，在小鼠的神经核（NAc），大脑结构，调节动机行为。药理学和遗传学实验表明，大麻素动员和随后的CB1大麻素受体的激活是必要的，足以表达社会互动的奖励特性，使用社会条件位置偏好测试进行评估。我们进一步表明，催产素，一种神经肽，加强父母和社会的纽带，驱动anandamide动员在NAC。催产素受体的药理学阻断停止这种反应，而化学发生，在下丘脑室旁核的催产素神经元的位点选择性激活刺激it.Genetic或药理学中断anandamide降解抵消催产素受体阻断对社会位置偏好和cFos在NAc的表达的影响。结果表明，在CB1受体的anandamide介导的信号，由催产素驱动，控制社会奖励。这种信号传导机制的缺陷可能会导致自闭症谱系障碍的社会障碍，并可能提供治疗这些疾病的途径。
Marijuana exerts profound effects on human social behavior, but the neural substrates underlying such effects are unknown. Here we report that social contact increases, whereas isolation decreases, the mobilization of the endogenous marijuana-like neurotransmitter, anandamide, in the mouse nucleus accumbens (NAc), a brain structure that regulates motivated behavior. Pharmacological and genetic experiments show that anandamide mobilization and consequent activation of CB1 cannabinoid receptors are necessary and sufficient to express the rewarding properties of social interactions, assessed using a socially conditioned place preference test. We further show that oxytocin, a neuropeptide that reinforces parental and social bonding, drives anandamide mobilization in the NAc. Pharmacological blockade of oxytocin receptors stops this response, whereas chemogenetic, site-selective activation of oxytocin neurons in the paraventricular nucleus of the hypothalamus stimulates it. Genetic or pharmacological interruption of anandamide degradation offsets the effects of oxytocin receptor blockade on both social place preference and cFos expression in the NAc. The results indicate that anandamide-mediated signaling at CB1 receptors, driven by oxytocin, controls social reward. Deficits in this signaling mechanism may contribute to social impairment in autism spectrum disorders and might offer an avenue to treat these conditions.