Background: New research is dramatically altering our understanding of the molecular mechanisms underlying neuronal communication.
Aim: To elucidate the molecular mechanisms underlying the therapeutic effects of mood stabilizers.
Method: Results from integrated clinical and laboratory studies are reviewed.
Results: Chronic administration of lithium and valproate produced a striking reduction in protein kinase C (PKC) isozymes in rat frontal cortex and hippocampus. In a small study, tamoxifen (also a PKC inhibitor) had marked antimanic efficacy. Both lithium and valproate regulate the DNA binding activity of the activator protein I family of transcription factors. Using mRNA differential display, it was also shown that chronic administration of lithium and valproate modulates expression of several genes. An exciting finding is that of a robust elevation in the levels of the cytoprotective protein, bcl-2.
Conclusions: The results suggest that regulation of signalling pathways may play a major part in the long-term actions of mood stabilizers. Additionally, mood stabilizers may exert underappreciated neuroprotective effects.