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Br J Psychiatry Suppl. 2001 Jun;41:s107-19.

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

Author information

  • 1Laboratory of Molecular Pathophysiology, Wayne State University School of Medicine, Detroit, Michigan, USA. manjih@intra.nimh.nih.gov

Abstract

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.

PMID:
11450170
[PubMed - indexed for MEDLINE]
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