Effect of androgen receptor blockade on spatial memory in young and aged male rats in the Barnes maze

Abstract

Spatial memory declines with age, and this decline is associated with decreased testosterone levels. However, the specific role of the androgen receptor in spatial memory performance in both young and aged rats remains largely unexplored. Our study aimed to investigate the effects of chronic androgen receptor blockade on spatial memory performance in young and aged male rats. Young (3 months old) and aged (21 months old) Wistar rats were assigned to one of three experimental groups: control, vehicle-, or flutamide-treated (10 mg/kg SC for 14 days). Spatial memory was evaluated using the Barnes maze (Days 8–14 of flutamide administration). The phases of spatial memory acquisition (4 daily trials/4 days) and retention (1 trial/day, 3 days after acquisition) were evaluated. The results indicated that older animals took longer to find the goal, traveled greater distances, and moved more slowly than their younger counterparts in the Barnes maze, regardless of treatment. During the acquisition phase, flutamide administration delayed learning in both young and aged animals. Specifically, flutamide-treated animals exhibited delayed learning during the assessment of overnight forgetting (trial 1 on each day of the acquisition phase). During the retention phase, an age-related effect was observed in the flutamide-treated groups. These findings suggest that androgen receptor blockade induces cognitive deficits in both young and aged male rats, supporting the modulatory role of endogenous androgens in memory function.