CB1 receptor antagonism in capuchin monkeys alters social interaction and aversive memory extinction

The endocannabinoid system (eCS) is an important modulator of social anxiety and social reward, as well as memory functions.

The present study evaluated the role of eCS in social interactions and aversive memory extinction in capuchin monkeys (Sapajus spp.) by blocking the cannabinoid type 1 receptor (CB_1r).

In experiment 1, spontaneous social and non-social behaviors of five capuchin males, each one living in triads with two other females, were observed after AM251 treatment (vehicle, 0.3, 1.0, and 3.0 mg/kg; i.m.). In experiment 2, seven male capuchin monkeys were trained to reach for a reward inside a wooden box. After training, they were given either vehicle or a 3.0-mg/kg i.m. dose of AM251 before a single aversive encounter with a live snake in the box. The latency to return to reach the reward inside the box in subsequent trials was measured.

The 3.0-mg/kg dose significantly increased the time spent performing self-directed behaviors, while decreasing that of social interactions. No changes were observed in vigilance or locomotion. AM251 increased the latency to reach the reward after the aversive encounter.

Taken together, these results suggest that CB_1r antagonism induces social deficits without increasing anxiety levels and impairs the extinction of aversive memories. This behavioral profile in monkeys underscores the potential involvement of eCS signaling in the deficits observed in autism spectrum disorders.