Induction of Anxiety-Like Phenotypes by Knockdown of Cannabinoid Type-1 Receptors in the Amygdala of Marmosets.

The amygdala is an important hub for regulating emotions and is involved in the pathophysiology of many mental diseases, such as depression and anxiety. Meanwhile, the endocannabinoid system plays a crucial role in regulating emotions and mainly functions through the cannabinoid type-1 receptor (CB 1 R), which is strongly expressed in the amygdala of non-human primates (NHPs). However, it remains largely unknown how the CB 1 Rs in the amygdala of NHPs regulate mental diseases. Here, we investigated the role of CB 1 R by knocking down the cannabinoid receptor 1 (CNR1) gene encoding CB 1 R in the amygdala of adult marmosets through regional delivery of AAV-SaCas9-gRNA. We found that CB 1 R knockdown in the amygdala induced anxiety-like behaviors, including disrupted night sleep, agitated psychomotor activity in new environments, and reduced social desire. Moreover, marmosets with CB 1 R-knockdown had up-regulated plasma cortisol levels. These results indicate that the knockdown of CB 1 Rs in the amygdala induces anxiety-like behaviors in marmosets, and this may be the mechanism underlying the regulation of anxiety by CB 1 Rs in the amygdala of NHPs.