Induction of Anxiety-Like Phenotypes by Knockout of Cannabinoid Type-1 Receptor in Amygdala of Marmosets

The amygdala is an important hub for the regulation of emotions, which is crucial for elucidating cellular and molecular mechanisms of many mental diseases. In the central nervous system, the endocannabinoid system plays a key role in the regulation of emotions and mainly functions through the cannabinoid type-1 receptor (CB1R), which is encoded by the Cnr1 gene. Although CB1R is highly expressed in the amygdala of non-human primates, little is known about its function. Here, we investigated the function of CB1R by knocking out the CB1R in the amygdala of adult marmosets through regional delivery of AAV-SaCas9-gRNA. We found that CB1R knockout in the amygdala of marmosets induced anxiety-like behaviors, including disrupted night sleep, agitated psychomotor activity in new environments, and reduced social desire, but had no effect on hedonic state and fear response. Moreover, CB1R-knockout marmosets exhibited up-regulated plasma cortisol levels, suggesting increased stress. These results showed that knockout of CB1R in the amygdala induced anxiety-like phenotypes in marmosets and shed new light on the mechanisms underlying the regulation of anxiety by CB1R in the amygdala of non-human primates.