Dietary n-3 fatty acids selectively attenuate LPS-induced behavioral depression in mice

Systemic administration of bacterial lipopolysaccharide (LPS) induces a series of physiological and pathological alterations as well as behavioral depression in experimental animals. These alterations induced by LPS administration are known to be mediated by endogenous cytokines and arachidonate metabolites, which may be modulated by dietary n-3 fatty acids. Mice were fed a diet supplemented with n-3 or n-6 fatty acids for 4 weeks prior to LPS administration. Food-motivated behavior after intraperitoneal administration of LPS as compared with that before LPS administration was significantly depressed in the mice fed with the n-6 fatty-acid-rich diet (47% to 85% reduction; P<.05) but not significantly in the mice fed with the n-3 fatty-acid-rich diet. Depression of social exploration by intraperitoneal LPS administration in the n-3 fatty-acid-rich diet group (39% reduction vs. vehicle group) was significantly less in the n-6 fatty-acid-rich diet group (76% reduction vs. vehicle group; P<.05). The behavioral depressions induced by intracerebroventricular LPS injection were not significantly different between the two dietary groups (P=.60). The elevation of serum corticosterone and the hypoglycemic response following intraperitoneal LPS administration were not significantly different between the two dietary groups (P=.57 and P=.43, respectively). We demonstrate that dietary n-3 fatty acids attenuate behavioral depression in mice peripherally administered with LPS without affecting the increase in serum corticosterone and the decrease in serum glucose concentration.