Cyclic AMP responsive element binding protein phosphorylation and DNA binding is decreased by chronic lithium but not valproate treatment of SH-SY5Y neuroblastoma cells

Mood stabilizing drugs decrease central nervous system cyclic AMP signaling . We report here that chronic, but not acute treatment with lithium chlorid e in human neuroblastoma SH-SY5Y cells, inhibits phosphorylation of cyclic AMP responsive element binding protein and cyclic AMP responsive element DN A binding induced by the adenylyl cyclase activator forskolin, bur has no e ffect on constitutive expression of cyclic AMP responsive element binding p rotein. These results are consistent with an effect of lithium to blunt the cyclic AMP signal transduction pathway. Such an effect is not shared by th e other commonly prescribed mood stabilizer, sodium valproate. Our results suggest that cyclic AMP responsive element binding protein regu lated gene expression may be relevant to the long-term prophylactic effect of lithium. Furthermore, sodium valproate, which is also effective in bipol ar disorder, would appear to act on other pathways to bring about its thera peutic effects. (C) 1999 IBRO. Published by Elsevier Science Ltd.