Bipolar disorder is a severe mental illness affecting 1-1.5% of the population.The pharmacotherapy of bipolar disorder utilizes a wide spectrum of mood-modulating drugs, including mood stabilizers, antidepressants and antipsychotic drugs.The mechanism(s) underlying the therapeutic effects of these drugs is not fully understood and the pathophysiology of bipolar disorder is not known.Accumulating evidence suggests that inflammation plays a role in the pathogenesis of bipolar disorder.Consistently, mood-modulating drugs were shown to exhibit anti-inflammatory properties and anti-inflammatory drugs were found efficacious in clinical trials of mood disorders.However, conflicting findings have also been reported.We have shown that lithium (the gold standard treatment of bipolar disorder) inhibits lipopolysaccharide (LPS)-induced inflammation in rat primary glia cells in a dose-dependent manner.Lithium inhibited LPS-induced secretion of inflammatory mediators such as tumor necrosis factor-(TNF-), interleukin 1-, prostaglandin E2 and nitric oxide (NO), and reduced the expression of inflammatory-associated enzymes such as cyclooxygenase-2 and inducible NO synthase.Moreover, recent data indicate that antipsychotic drugs (e.g., olanzapine and haloperidol) alter inflammatory responses both in-vitro and in-vivo.Furthermore, our preliminary data postulate that anti-TNF-treatment possess antidepressant-like effect in rats.Taken together, these findings suggest that inflammation plays a role in the pathophysiology of bipolar disorder and that anti-inflammatory strategies may be a useful treatment for mood disorders.Other researchers who contributed to the data that will be presented are: Sigalit Nahman (M.Sc.), RH Belmaker (M.D.) and Caroline Fauor (BN).