This study was conducted to determine if alpha-tocopherol facilitates recovery from lipopolysaccharide (LPS)-induced sickness behavior through a NFkappaB-dependent mechanism. In the first study, 3 daily intraperitoneal (i.p.) injections of alpha-tocopherol (20 mg) improved recovery from sickness behavior induced by i.p. injected LPS. Furthermore, alpha-tocopherol pretreatment attenuated LPS-activated NFkappaB and pro-inflammatory cytokine production in brain. In addition, inhibiting NFkappaB activity in the brain specifically by ICV injection of a NFkappaB decoy prior to LPS, significantly accelerated recovery from LPS-induced sickness behavior. Taken together, these data indicate alpha-tocopherol modulates sickness behavior and inflammatory cytokine production in the brain through an NFkappaB-dependent pathway.
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