Short-Term Fish Oil Supplementation during Adolescence Supports Sex-Specific Impact on Adulthood Visuospatial Memory and Cognitive Flexibility

Numerous studies have supported benefits of omega-3 supplementation using Menhaden fish oil (FO) to promote brain maturation and plasticity during critical developmental periods. The goal of this study was to determine sex-specific immediate and delayed impact of adolescent omega-3 supplementation on visuospatial memory and cognitive flexibility. Sixty-four Wistar rats (n = 32 males and females) received daily FO or soybean oil (CSO) supplementation via oral gavage (0.3 mL/100 g body weight) from postnatal day 28–47. The Barnes Maze Test (BMT) was used to measure visuospatial memory and reversal learning trials (RL) determined cognitive flexibility. Juveniles underwent testing immediately after the gavage period, while adults began testing on postnatal day 90. Adult rats showed reduced working memory errors (WME) and gradual decrease in escape latencies compared to juveniles. Importantly, adult FO-supplemented females displayed fewer WME than males, while males’ performance benefited from CSO supplementation. Overall, sex- and supplementation-dependent effects supported a positive impact of FO in female rats only. Our findings support the potential for supplementation limited to the early adolescence period to influence adulthood spatial learning and cognitive flexibility in a sex-specific manner.