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Effects of chronic lithium and carbamazepine treatment on G-protein subunit expression in rat cerebral cortex

  • Peter P. Li
    Correspondence
    Address reprint requests to Peter P. Li, Ph.D., Section of Biochemical Psychiatry, Clarke Institute of Psychiatry, 250 College Street, Toronto, Ontario, M5T 1R8.
    Footnotes
    Affiliations
    From the Section of Biochemical Psychiatry, Clarke Institute of Psychiatry, University of Toronto, Toronto, Ontario Canada

    Department of Pharmacology, University of Toronto, Toronto, Ontario Canada
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  • L.Trevor Young
    Footnotes
    Affiliations
    From the Section of Biochemical Psychiatry, Clarke Institute of Psychiatry, University of Toronto, Toronto, Ontario Canada

    Institute of Medical Sciences, University of Toronto, Toronto, Ontario Canada
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  • Ying K. Tam
    Footnotes
    Affiliations
    From the Section of Biochemical Psychiatry, Clarke Institute of Psychiatry, University of Toronto, Toronto, Ontario Canada
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  • David Sibony
    Footnotes
    Affiliations
    From the Section of Biochemical Psychiatry, Clarke Institute of Psychiatry, University of Toronto, Toronto, Ontario Canada
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  • Jerry J. Warsh
    Footnotes
    Affiliations
    From the Section of Biochemical Psychiatry, Clarke Institute of Psychiatry, University of Toronto, Toronto, Ontario Canada

    Department of Pharmacology, University of Toronto, Toronto, Ontario Canada

    Institute of Medical Sciences, University of Toronto, Toronto, Ontario Canada
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  • Author Footnotes
    ∗ We are indebted to Dr. R.R. Reed for supplying the cDNA clones for 11, 11, 12, and 0; Dr. T. Kozasa for the x cDNA; and Dr. M. Levine for the 1−3 cDNA clones.
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      Abstract

      Although lithium and carbamazepine (CBZ) are effective in the treatment of bipolar affective disorder, their mechanism of action is still unknown. Recent evidence suggests that lithium and CBZ might exert their therapeutic effects by modulating the function of guanosine triphosphate (GTP)-regulatory (G) proteins associated with central nervous system second messenger systems. In the present study, we showed that chronic lithium administration decreases 3, 11, and 12 messenger RNA (mRNA) abundance by 25%–30% in rat cerebral cortex. However, the levels of 3, 11, and 12 mRNA were unaffected by chronic CBZ treatment. The effects of lithium on 3, 11, and 12 mRNA levels appear to be selective, as the mRNA levels of o, x, 1, and 3 subunits remained unchanged. Two days after terminating chronic lithium treatment, changes in 3, 11, and 12 mRNA levels were not demonstrable. Short-term administration of lithium (2 days), however, reduced only the 12 mRNA levels. Surprisingly, there was no significant difference in the amount of immunologically detectable 3−3, 3−1, i(1+2), 0, and (1+2) in the cortex of rats chronically treated with lithium or CBZ, compared with controls. These data suggest that the effects of chronic lithium on s, 11, and 12 mRNA levels are not shared by CBZ, although both treatments are known to be efficacious in bipolar affective disorder. Furthermore, the data suggest that lithium may modify G-protein functionality through the regulation of the genes expressing G-protein isoforms. However, this effect on G-protein expression appears complex and may be accompanied by compensatory posttranslational regulation of G-protein turnover.

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