Key result
Administration of therapeutic doses of lithium, valproate, or neuroleptics did not alter GSK-3 protein levels or activity in the rat frontal cortex.
Why the study?
Do mood stabilizers or neuroleptics alter GSK-3 protein levels and activity in the rat frontal cortex?
Do mood stabilizers or neuroleptics alter GSK-3 protein levels and activity in the rat frontal cortex?
Mood stabilizers and neuroleptics do not alter GSK-3 protein levels or activity in the rat frontal cortex, suggesting that the reduction of GSK-3 seen in schizophrenic patients is not related to neuroleptic treatment.
No support for medication effects on cortical GSK-3; leaves open non-treatment mechanisms for reductions observed in schizophrenia.
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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Kozlovsky et al. (2003) studied Schizophrenia (animal model relevance). Lithium, valproate, haloperidol, chlorpromazine, or clozapine was evaluated on GSK-3 protein levels and GSK-3 activity in the frontal cortex. Administration of therapeutic doses of lithium, valproate, or neuroleptics did not alter GSK-3 protein levels or activity in the rat frontal cortex.
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