CB1 receptor antagonism reverses social and cognitive deficits induced by repeated exposure to distressed conspecifics in rats

Empathy is a behavioral phenomenon characterized by the capacity to share in another individual’s distressing experiences, including pain, discrimination, and social rejection. The cannabinoid system, recognized as one of the brain’s neuromodulatory systems, appears to play a significant role in social and prosocial behaviors, particularly in the context of empathy. This study aimed to investigate the potential role of the cannabinoid system in mediating empathic pain and behavior, an area that has not been thoroughly explored to date. To this end, an empathic pain model was employed, wherein pain was socially transmitted from a sibling demonstrator, who received five formalin injections, to a sibling observer. Naïve observer rats were administered either the cannabinoid type 1 receptor (CB1R) antagonist rimonabant (1 mg/kg, i.p.) or the CB1R agonist WIN 55,212–2 (WIN; 3 mg/kg, i.p.) 30 min prior to behavioral assessments. The animals were subsequently evaluated using tail-flick and social interaction tasks. The behavioral findings revealed that both the demonstrator and observer groups exhibited significant increases in hyperalgesia and impairments in social memory. Notably, the administration of rimonabant, but not WIN, partially restored cognitive functions and induced analgesia in the observer rats. Furthermore, hippocampal levels of brain-derived neurotrophic factor (BDNF) decreased in both demonstrator and observer rats, whereas rimonabant administration resulted in an increase in BDNF levels in the hippocampus, in contrast to WIN. These results suggest that the CB1R may be intricately involved in prosocial behavior and emotional contagion, potentially through the modulation of BDNF levels in the hippocampus.