Agmatine attenuates lipopolysaccharide induced anorexia and sickness behavior in rats

Sickness behavior is characterized by lethargy, reduced appetite, anhedonia and anxiety. It can be induced in experimental animals by bacterial endotoxin, lipopolysaccharide (LPS). We investigated the impact of intracerebroventricular agmatine injections (5-20 μg/rat, icv) on sickness behavior induced by LPS (100 μg/rat, ip) in rats. Rats challenged with LPS demonstrated hyperthermia, anorexia, anxiety, depression like phenomenon and reduction in body weights. Additionally, mediators of sickness behaviors, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) level in LPS treated rat serum were also increased. The present study revealed that these LPS induced symptoms of sickness behavior including anorexia were normalized by pretreatment with agmatine. The IL-6 and TNF-α serum levels were also normalized in agmatine pretreated rats. It is anticipated that agmatine may suppress LPS induced sickness behavior by inhibiting proinflammatory pathway and/or activity circuitry in brain. This study suggests that agmatine may be an important therapeutic target in the treatment of anorexia and other neurological abnormalities associated with bacterial infection.