Clinical and preclinical findings have suggested a role of the endocannabinoid system (ECS) in the etiopathology of autism spectrum disorder (ASD). Previous mouse studies have investigated the role of ECS in several behavioral domains; however, none of them has performed an extensive assessment of social and communication behaviors, that is, the main core features of ASD. This study employed a mouse line lacking the primary endocannabinoid receptor (CB1r) and characterized ultrasonic communication and social interaction in CB1^−/−, CB1^+/−, and CB1^+/+ males and females. Quantitative and qualitative alterations in ultrasonic vocalizations (USVs) were observed in CB1 null mice both during early development (i.e., between postnatal days 4 and 10), and at adulthood (i.e., at 3 months of age). Adult mutants also showed marked deficits in social interest in the three-chamber test and social investigation in the direct social interaction test. These behavioral alterations were mostly observed in both sexes and appeared more marked in CB1^−/− than CB1^+/− mutant mice. Importantly, the adult USV alterations could not be attributed to differences in anxiety or sensorimotor abilities, as assessed by the elevated plus maze and auditory startle tests. Our findings demonstrate the role of CB1r in social communication and behavior, supporting the use of the CB1 full knockout mouse in preclinical research on these ASD-relevant core domains.

中文翻译：

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大麻素 1 型受体缺失小鼠的交流和社会互动：对自闭症谱系障碍的影响

临床和临床前研究结果表明内源性大麻素系统 (ECS) 在自闭症谱系障碍 (ASD) 的病因病理学中的作用。以前的小鼠研究已经调查了 ECS 在几个行为领域中的作用。然而，他们都没有对社交和交流行为进行广泛的评估，即 ASD 的主要核心特征。本研究采用缺乏主要内源性大麻素受体 ( CB1 r) 的小鼠品系，并在CB1 ^-/-、CB1 ^+/-和CB1 ^+/+雄性和雌性中表征超声波通信和社会互动。在CB1中观察到超声波发声 (USV) 的定量和定性变化在早期发育期间（即出生后第 4 天和第 10 天之间）和成年期（即 3 个月大），无效小鼠。成年突变体在三室测试和直接社会互动​​测试中的社会调查中也表现出明显的社会兴趣缺陷。这些行为改变主要在两性中观察到，并且在CB1 ^-/-中比在CB1 ^+/-突变小鼠中更为明显。重要的是，成人 USV 的改变不能归因于焦虑或感觉运动能力的差异，正如通过高架十字迷宫和听觉惊吓测试所评估的那样。我们的研究结果证明了 CB1r 在社会交流和行为中的作用，支持使用CB1在这些 ASD 相关核心域的临床前研究中完全敲除小鼠。