Acute lithium treatment enhances neuropeptide Y gene expression in rat hippocampus

It has been suggested that the therapeutic action of lithium in affective disorders may be due to its inhibition of signal transduction and second messenger synthesis, in particular of the phosphoinositide (PI) pathway. Yet, previous work in neuronal cell lines indicates that lithium has an enhancing effect on gene expression mediated by protein kinase C, which is activated by the PI pathway. In this report, we have analyzed the effect of lithium on two neuropeptide encoding genes that are regulated by second messenger systems; neuropeptide Y (NPY) and proenkephalin (Enk). We find that acute treatment with lithium, resulting in serum levels that are within the therapeutic range effective in patients with mood disorders, significantly enhances basal expression of the NPY gene in rat hippocampus. In contrast, no effect on Enk expression was detected. This selective effect in a limbic structure supports the hypothesis that gene expression may be an important target of lithium's therapeutic action.