Nicotine dependence is causally linked to increased risk of mood/anxiety disorders in later life. Females are reported to experience a higher prevalence of anxiety/depressive disorders and challenges in smoking cessation therapies, suggesting a potential sex-specific response to nicotine exposure and mood/anxiety disorder risk. However, pre-clinical evidence of sex-specific responses to adolescent nicotine exposure is unclear. Thus, to determine any sex differences in anxiety/depressive-related outcomes, adolescent male and female Sprague Dawley rats received nicotine (0.4 mg/kg; 3x daily) or saline injections for 10 consecutive days, followed by behavioural testing, in-vivo electrophysiology and Western Blot analyses. Our results revealed that adolescent nicotine exposure caused long-lasting anxiety/depressive-like behaviours, disrupted neuronal activity patterns and molecular signaling pathway targets in nicotine-treated male rats, but no significant effects in female cohorts, suggesting possible compensatory actions related to estrogen/progesterone signaling pathways in female. These novel results serve as a foundation for future investigations examining how adolescent nicotine exposure may differentially impact the male vs. female brains
