Rudolf Magnus Institute of Neuroscience, Department of Neuroscience and Pharmacology, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands.
J Neurosci. 2012 Oct 24;32(43):14899-908. doi: 10.1523/JNEUROSCI.0114-12.2012.
The brain endocannabinoid system plays a crucial role in emotional processes. We have previously identified an important role for endocannabinoids in social play behavior, a highly rewarding form of social interaction in adolescent rats. Here, we tested the hypothesis that endocannabinoid modulation of social play behavior occurs in brain regions implicated in emotion and motivation. Social play increased levels of the endocannabinoid anandamide in the amygdala and nucleus accumbens (NAc), but not in prefrontal cortex or hippocampus of 4- to 5-week-old male Wistar rats. Furthermore, social play increased phosphorylation of CB1 cannabinoid receptors in the amygdala. Systemic administration of the anandamide hydrolysis inhibitor URB597 increased social play behavior, and augmented the associated elevation in anandamide levels in the amygdala, but not the NAc. Infusion of URB597 into the basolateral amygdala (BLA) increased social play behavior, and blockade of BLA CB1 cannabinoid receptors with the antagonist/inverse agonist SR141716A prevented the play-enhancing effects of systemic administration of URB597. Infusion of URB597 into the NAc also increased social play, but blockade of NAc CB1 cannabinoid receptors did not antagonize the play-enhancing effects of systemic URB597 treatment. Last, SR141716A did not affect social play after infusion into the core and shell subregions of the NAc, while it reduced social play when infused into the BLA. These data show that increased anandamide signaling in the amygdala and NAc augments social play, and identify the BLA as a prominent site of action for endocannabinoids to modulate the rewarding properties of social interactions in adolescent rats.
大脑内源性大麻素系统在情绪过程中起着至关重要的作用。我们之前已经确定内源性大麻素在青少年大鼠的社交游戏行为中起着重要作用，社交游戏行为是一种高度有益的社交互动形式。在这里，我们测试了这样一个假设，即内源性大麻素对社交游戏行为的调节作用发生在与情绪和动机相关的大脑区域。社交游戏增加了 4-5 周龄雄性 Wistar 大鼠杏仁核和伏隔核（NAc）中的内源性大麻素大麻素 1 型受体（CB1）的磷酸化水平。此外，社交游戏增加了杏仁核中的内源性大麻素大麻素 1 型受体（CB1）的磷酸化水平。内源性大麻素水解抑制剂 URB597 的全身给药增加了社交游戏行为，并增强了与杏仁核中内源性大麻素水平升高相关的作用，但对 NAc 没有影响。URB597 注入外侧杏仁核（BLA）增加了社交游戏行为，而拮抗剂/反向激动剂 SR141716A 阻断 BLA 中的 CB1 大麻素受体则阻止了 URB597 全身给药的增强作用。URB597 注入 NAc 也增加了社交游戏，但阻断 NAc 中的 CB1 大麻素受体并不能拮抗 URB597 全身处理的增强作用。最后，SR141716A 注入 NAc 的核心和壳亚区后不会影响社交游戏，而注入 BLA 则会减少社交游戏。这些数据表明，杏仁核和 NAc 中内源性大麻素信号的增加增强了社交游戏行为，并确定了外侧杏仁核作为内源性大麻素调节青少年大鼠社交互动奖赏特性的突出作用部位。
