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. 2011 Nov;16(11):1068-70.
doi: 10.1038/mp.2011.47. Epub 2011 Apr 19.

Inhibition of glycogen synthase kinase-3 is necessary for the rapid antidepressant effect of ketamine in mice

E Beurel, L Song, R S Jope

Inhibition of glycogen synthase kinase-3 is necessary for the rapid antidepressant effect of ketamine in mice

E Beurel et al. Mol Psychiatry. 2011 Nov.
No abstract available

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Figures

Figure 1
Figure 1
Ketamine rapidly increases inhibitory serine-phosphorylation of glycogen synthase kinase-3 (GSK3), which is required for its antidepressant effect in the learned helplessness model of depression-like behavior in mice. (a) The inhibitory serine-phosphorylation of GSK3α (on serine-21) and GSK3β (on serine-9) was increased in the hippocampus and cerebral cortex 30 and 60 min after administration of 10 mg kg−1 ketamine (i.p.). Total levels of GSK3α and GSK3β were unaltered by ketamine treatment, indicating ketamine modulates phosphorylation, not expression, of GSK3. (b) The learned helplessness model of depression-like behavior was tested as described by Li et al. Wild-type (WT) or GSK3 knock-in (KI) mice were subjected to random mild foot shocks, 24 h later ketamine (K; 10 mg kg−1; i.p.) or lithium chloride (Li; 100 mg kg−1; i.p.) was administered, and after 24 h mice were tested with escapable foot shocks. The number of failures to escape out of 30 trials from the escapable foot shocks and the 5-trial average latency to escape in 24 s trials are shown. Comparisons (*P < 0.05; analysis of variance) demonstrate that ketamine significantly increased serine-phosphorylation of GSK3 and ketamine and lithium significantly reduced depression-like behaviors in wild-type mice, whereas ketamine was ineffective in GSK3 knock-in mice in which serine-phosphorylation of GSK3 is blocked.
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