Lack of effect of mood stabilizers or neuroleptics on GSK-3 protein levels and GSK-3 activity.
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.
Kozlovsky
Nitsan
N
Stanley Research Center, Ben Gurion University of the Negev and Mental Health Center, Beersheva, Israel.
Nadri
Carmit
C
Belmaker
Robert H
RH
Agam
Galila
G
D000339:Affect / Q000187:drug effects*; D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002746:Chlorpromazine / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000096:biosynthesis*; D000071679:Glycogen Synthase Kinase 3 beta; D006220:Haloperidol / Q000494:pharmacology; D008094:Lithium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014635:Valproic Acid / Q000494:pharmacology
D018692:Antimanic Agents; D014150:Antipsychotic Agents; D014635:Valproic Acid; D008094:Lithium; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D003024:Clozapine; D006220:Haloperidol; D002746:Chlorpromazine