Chronic cannabidiol administration modulates depressive and cognitive alterations induced by social isolation in male mice

Cannabidiol (CBD), a non-psychotropic compound derived from Cannabis sativa, is known for its potential therapeutic effects on central nervous system (CNS) disorders. This study investigates the effects of chronic CBD administration on depressive and cognitive alterations induced by social isolation in male C57BL/6 mice. The experimental design involved adult mice subjected to either group housing or 12 weeks of social isolation. Behavioral assessments, including the sucrose preference test, open field test, light/dark box, novel object recognition, and tail suspension test, were performed to evaluate the impact of CBD on emotional and cognitive alterations. Additionally, hippocampal gene expression for cannabinoid type 1 receptors (CB1R), serotonin type 1A receptors (5HT1AR), and brain-derived neurotrophic factor (BDNF) were analyzed. Results indicate that CBD mitigated anhedonia in isolated mice and reduced immobility episodes in the TST. However, CBD did not exert significant anxiolytic effects and unexpectedly induced anxiety-like behavior in group-housed mice. The study also revealed that social isolation impaired recognition memory and reduced BDNF expression, while CBD treatment protected memory in isolated mice. These findings suggest that CBD has potential antidepressant and neuroprotective effects in social isolation-induced depressive models, although its anxiogenic effects in non-stressed mice warrant further investigation.