Effects of chronic lithium and carbamazepine treatment on G-protein subunit expression in rat cerebral cortex.
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 G alpha s, G alpha i1, and G alpha i2 messenger RNA (mRNA) abundance by 25%-30% in rat cerebral cortex. However, the levels of G alpha s, G alpha i1, and G alpha i2 mRNA were unaffected by chronic CBZ treatment. The effects of lithium on G alpha s, G alpha i1, and G alpha i2 mRNA levels appear to be selective, as the mRNA levels of G alpha o, G alpha x, G beta 1, G beta 2, and G beta 3 subunits remained unchanged. Two days after terminating chronic lithium treatment, changes in G alpha s, G alpha i1, and G alpha i2 mRNA levels were not demonstrable. Short-term administration of lithium (2 days), however, reduced only the G alpha i2 mRNA levels. Surprisingly, there was no significant difference in the amount of immunologically detectable G alpha s-s, G alpha s-1, G alpha i(1 + 2), G alpha 0, and G beta (1 + 2) in the cortex of rats chronically treated with lithium or CBZ, compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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Section of Biochemical Psychiatry, Clarke Institute of Psychiatry, Toronto, Ontario, Canada.
Young
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Tam
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Sibony
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Warsh
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D000818:Animals; D001345:Autoradiography; D015153:Blotting, Western; D002220:Carbamazepine / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000276:immunology; D019204:GTP-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D012333:RNA, Messenger / Q000187:drug effects* / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar
D012333:RNA, Messenger; D002220:Carbamazepine; D008094:Lithium; D019204:GTP-Binding Proteins