Role of GSK3β in behavioral abnormalities induced by serotonin deficiency

Abstract

We were interested to read the article by Beaulieu et al. (1), suggesting that GSK3β haploinsufficiency counteracts depressive-like behavior in mice expressing a functional TPH2 mutant with a marked decrease in serotonin production. In the figures of the current article, it is clear that GSK3β haploinsufficiency had no antidepressant effect in the tail suspension test in animals without the TPH2 mutant enzyme. However, Beaulieu et al. fail to mention the paper by O'Brien et al. (2), who reported that GSK3β haploinsufficiency alone gives dramatic antidepressant-like effects in the Porsolt swim test, a closely related test for antidepressant behavior. We also have not been able to replicate the results of Beaulieu et al. (see ref. 3). However, it would have seemed essential for the discussion of the current Beaulieu et al. article that they mention the previous report, which found that GSK3β haploinsufficiency is quite sufficient to cause an antidepressant phenotype, in contradiction to their own findings.