Lithium and valproate differentially regulate brain regional expression ofphosphorylated CREB and c-Fos

Previous studies in our laboratory have shown that the mood stabilizers, li thium and valproate (VPA), regulate the transcription factors, cyclic AMP r esponsive element binding protein (CREB), c-Fos and c-Jun, differentially i n cultured human neuroblastoma SH-SY5Y cells. Here, we confirm these findin gs in rat brain and further study the brain-regional effects of these drugs using immunohistochemistry. We found that although chronic treatment with LiCl or VPA did not change the expression of c-Fos and c-Jun, acute treatme nt with either drugs increased c-Fos expression but not c-Jun expression in CA1 and CA3 regions of hippocampus. Chronic treatment with LiCl, but not V PA, decreased CREB phosphorylation in rat cerebral cortex and hippocampus. These results suggest that lithium and VPA may act on different pathways to bring about their long-term prophylactic effects on bipolar disorder (BD). The regulation of CREB phosphorylation may be relevant to lithium effect. VPA, which is also effective in ED, may be linked to other pathways. (C) 19 99 Published by Elsevier Science B.V. All rights reserved.