Lack of effect of mood stabilizers or neuroleptics on GSK-3 protein levels and GSK-3 activity.
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| Abstract |
Glycogen synthase kinase (GSK)-3 protein levels and GSK-3 activity were previously found to be over 40% reduced in the post-mortem prefrontal cortex of schizophrenic patients. Lithium and valproate have been reported to selectively inhibit GSK-3. We hypothesized that in-vivo administration of lithium and valproate would result in up-regulation of GSK-3 protein levels and GSK-3 activity. The present study aimed to evaluate the possible involvement of neuroleptic treatment in the decrease of GSK-3 in schizophrenia. Rat frontal cortex GSK-3 protein levels and GSK-3 activity were measured following administration of therapeutic doses of lithium or valproate for 11 d, or of haloperidol, chlorpromazine or clozapine for 21 d. None of the drugs induced a change in GSK-3 protein levels. All the drugs except chlorpromazine (which was not tested) did not affect GSK-3 activity. This suggests that GSK-3 inhibition by lithium or valproate does not induce regulation of protein levels or activity and that the reduction in GSK-3 protein levels and GSK-3 activity in the post-mortem prefrontal cortex of schizophrenic patients is not neuroleptic-treatment related.
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| Authors | Nitsan Kozlovsky, Carmit Nadri, Robert H Belmaker, Galila Agam |
| Journal | The international journal of neuropsychopharmacology (Int J Neuropsychopharmacol) Vol. 6 Issue 2 Pg. 117-20 (Jun 2003) ISSN: 1461-1457 [Print] England |
| PMID | 12890304 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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