Chronic dietary lithium inhibits basal c-fos mRNA expression in rat brain

1. Lithium is the most effective prophylactic agent used in the treatment of bipolar disorder. Although the acute effects of lithium include an inhibitory action on the phosphatidylinositol (PI) system, the longer term effects on signal transduction processes linked to this system are poorly understood. 2. An important consequence of activation of receptors linked to the PI pathway is activation of protein kinase C (PKC), which is involved in the induction of the proto-oncogene, c-fos. 3. The authors hypothesized that chronic lithium treatment, by inhibiting signaling through the PI/PKC pathway, might alter the expression of fos. 4. It was found that basal expression of c-fos was significantly reduced in cortical, hippocampal and hypothalamic brain areas of rats fed dietary lithium for 4 weeks. 5. The present results suggest that some of the effects of chronic lithium treatment may be mediated by alterations in signal transduction mechanisms linked to fos expression.