Modulatory Effects of CB1 Receptors on Cognitive Performance in Rat Model of Empathic Pain

Cannabinoid receptor type 1 (CB1) is extensively distributed across brain regions that are crucial for emotional processing, social cognition, and anxiety, including the prefrontal cortex, amygdala, and hippocampus. Dysregulation of CB1 receptors (CB1Rs) has been associated with several disorders characterized by impaired empathy, social behavior, and anxiety. Accordingly, this study investigates the modulatory role of CB1Rs in social interaction and anxiety in an empathic pain model in rats.

A total of 48 adult male Wistar rats were used (n=8 for each group). One sibling received formalin injection into the hind paw five times within nine days (demonstrator), and the other siblings reported pain (observer) while being treated with dimethyl sulfoxide (DMSO), the CB1R agonist WIN 55,212-2 (WIN; 3 mg/kg, intraperitoneal), or the CB1R antagonist rimonabant (1 mg/kg intraperitoneal). Treatments were administered intraperitoneally 30 min before behavioral tests conducted on day 10, which were used to assess social behavior and anxiety.

Empathic pain can impair social behavior and elicit anxiety-like effects. Rimonabant was effective in ameliorating deficits induced by empathic pain; conversely, WIN did not have a significant effect.

CB1Rs play a modulatory role in social contagion. This modulation may provide new therapeutic targets for conditions, such as autism spectrum disorder, schizophrenia, and other psychological disorders characterized by impaired empathy and dysregulated social behavior associated with the CB1 signaling pathway.