Lithium, but not valproate, induces the serine/threonine phosphatase activity of protein phosphatase 2A in the rat brain, without affecting its expression.

Protein phosphatase 2A (PP2A) regulates protein kinase cascades and thus plays an important role in the regulation of cell growth, gene expression and development. We examined the influence of lithium and valproate on the expression of PP2A and its serine/threonine phosphatase activity in the rat frontal cortex and hippocampus. Western blot and immunohistochemical analyses demonstrated that neither lithium nor valproate treatment had an effect on the levels of PP2A immunoreactivity in these brain regions. However, administration of lithium for 1 or 14 days significantly upregulated the activity of PP2A in the frontal cortex. Similarly, lithium administration tended to increase the activity of PP2A in the hippocampus. In contrast, neither a single nor repeated administration of valproate affected the activity of PP2A in these brain regions. These findings indicate that lithium, but not valproate, upregulated the activity of PP2A in the rat brain. It is suggested that the changes in neuronal functions induced by PP2A may be, at least in part, associated with the therapeutic action of lithium.