Cocaine use disorder is a chronic condition marked by a shift from sporadic to compulsive use. Such progression depends on environmental and biological factors. These factors act not only on neurobiological mechanisms but also on intercellular communication systems such as exosome synthesis. Our team aims to study the biological mechanisms linked to the Social isolation (SI)-induced cocaine sensitization in adolescent rats, where we evaluate the role of the Wnt canonical pathway by measuring the levels of β-catenin in Prefrontal Cortex (PFC), Nucleus accumbens (NAcc), Amygdala (Amy), and Caudate-Putamen (CP). Previously, we showed that changes in the Wnt canonical pathway are associated with both cocaine sensitization and adolescent SI. Here, we examined if 5 days of SI (PND30-35) would induce cocaine sensitization on PND45 and changes in β-catenin levels of reward-related brain regions, in female and male rats. The results revealed that SI induced cocaine (5mg/kg i.p.) sensitization only in male rats (p<0,05). Also, isolated males showed lower β-catenin levels in the PFC, higher levels in the NAcc after cocaine (p<0,05). In Amy, cocaine increased the levels of β-catenin (p<0,05), while no changes were found in CP. The behavioural findings were replicated in a new cohort of animals, and plasma samples were taken to isolate exosomes. The size, quantity, and brain-derived protein cargo will be analysed as putative systemic biomarkers of SI-induced cocaine vulnerability.