Long-term alterations in the endocannabinoid signaling system in brains of adult rats subjected to social isolation and handling

Social isolation, in rodents, produces psychopathological features that are reversed by handling. However, the neurochemical mechanisms underlying isolation rearing and handling remain poorly understood. Moreover, whether handling alters the endocannabinoid system (eCBS) is unknown. Therefore, we examined whether isolation rearing and handling alter the eCBS. We also evaluated whether handling would reverse isolation-induced eCBS perturbation. At weaning, rats were isolation or group reared and concomitantly handled or non-handled daily until adulthood. Cannabinoid receptor densities and endocannabinoid content were measured in brains from these rats using [3H]CP55,940 binding and quantitative autoradiography and lipid analysis. Isolation rearing altered cannabinoid receptor densities and endocannabinoid content. Handling altered both cannabinoid receptor densities and content in regions that control emotional expression compared to non-handling. Unlike group-, isolation-reared rats failed to exhibit handling-induced increases in both receptor densities and content. These data further implicate a pivotal role for the endocannabinoid system in adaptation to stress.