Emotion-Based Cognition in Mice Is Differentially Influenced by Dose and Chemical Form of Dietary Docosahexaenoic Acid

Docosahexaenoic acid (DHA) is a major constituent, and primary omega-3 fatty acid, in the brain. Evidence suggests that DHA consumption may promote cognitive functioning and prevent cognitive decline, and these effects may be particularly relevant in the context of fear or stress. However, the potency and efficacy of dietary DHA may depend on the form of DHA (e.g., phospholipid; PL vs. triglyceride; TG). In this study, we compared in mice the effects of consuming PL and TG forms of DHA on associative, avoidance (fear) based learning and memory. Diets consisted of either no DHA or 1%, 2%, and 4% PL- or TG-DHA. After 4 weeks on the test diets (n = 12/group), we used the 3-day passive avoidance (PA) and elevated plus maze (EPM) to examine fear and fear-associated learning and memory. We found a significant (p < 0.05) diet by time interaction in the PA and EPM. Compared to the control and the 1% TG-DHA group, mice consuming the diet supplemented with 1% PL-DHA displayed a significantly greater latency by test day 2 in the 3-day PA. No differences in latency between any of the groups were observed during trials 1 and 3. Mice consuming the 2% PL-DHA diet spent significantly more time frequenting the open arms during the first minute, but not the last 4 min, of the test. Compared to all other groups, mice fed the 4% TG-DHA diet had increased spleen, liver, and visceral fat weight. Consumption of the lower dose PL-DHA may confer enhanced efficacy, particularly on fear-based learning behavior.