Our previous study demonstrated that 5-HT_1A receptor activation by chronic administration of flesinoxan, a 5-HT_1A receptor agonist, reduces the abnormal emotionality in stress-maladaptive mice and promotes oligodendrogenesis and myelination. However, the effects of 5-HT_1A receptor activation on oligodendrocyte transcription factors under the stress-maladaptive situations and the underlying mechanisms remain unknown. In the present study, we investigated whether activation of 5-HT_1A receptor by flesinoxan could act on oligodendrocytes to induce oligodendrocyte transcription factors in stress-maladaptive mice. Western blot analysis revealed that administration of flesinoxan significantly increased the expression levels of Gab1 and p-GSK3β (Y216) in the hippocampus of stress-maladaptive mice, whereas decreased the expression level of p-GSK3β (Ser 9) in the same brain regions. Under this condition, the significant increase in mRNA expression levels of oligodendrocyte transcription factors, i.e. olig2, SOX10, MYF, NKX2.2 and Zfp24, in the hippocampus were observed by real-time PCR analysis. The present findings suggest that 5-HT_1A receptor activation may induce oligodendrocyte transcription factors via the hippocampal Gab1/GSK3β signaling pathway and reduce abnormal emotionality due to maladaptation to excessive stress.