Bipolar disorder: leads from the molecular and cellular mechanisms of action of mood stabilisers

Background New research is dramatically altering our understanding of the m olecular mechanisms underlying neuronal communication. Aim To elucidate the molecular mechanisms underlying the therapeutic effect s of mood stabilisers. 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 hip pocampus. In a small study, tamoxifen (also a PKC inhibitor) had marked ant imanic efficacy. Both lithium and valproate regulate the DNA binding activi ty of the activator protein I family of transcription factors, Using m RNA differential display. it was also shown that chronic administration of lith ium and valproate modulates expression of several genes. An exciting findin g 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 stabilisers. Additionall y mood stabilisers may exert underappreciated neuroprotective effects.