This study aims to explore the impact of social isolation on memory, learning and behavioral changes in middle aged Sprague Dawley (SD) and Wistar Albino (WIS) rat strains and to investigate cortical trace element levels, seeking potential correlations between these levels and the observed behavioral responses to social isolation. Four groups of 14-month-old male rats established: control and isolated SDs and WIS rats (CONT-SD, ISO-SD, CONT-WIS, ISO-WIS). Morris Water Maze (MWM) and Porsolt Forced Swimming (PFS) tests were conducted for behavioral assessment. Following behavioral tests, rats were sacrificed under general anesthesia, and cortices were isolated for analysis of macro and trace element levels (ICP/MS). MWM and PFS tests reveal that while CONT-SD rats outperform CONT-WIS in the MWM test, they exhibit increased depressive behaviors following social isolation (p < 0.05). For trace elements, ISO-SD rats showed elevated levels of Co and Cu, along with reduced levels of Cs and As, compared to ISO-WIS rats. Isolation leads to decreased Cu and Mo levels but increased Rb in WIS rats. Additionally, for control groups, lower Zn levels was found in WIS compared to SD rats. These results indicate that SD rats learn faster, have better memory function, yet are more susceptible to depression post-isolation. The increased Co and Cu levels in ISO-SD align with previous findings, suggesting potential trace element involvement in stress responses. Understanding these mechanisms could inform preventive strategies or therapeutic targets, contributing to research and interventions promoting a balanced diet to alleviate neurobehavioral abnormalities associated with social isolation.