Chronic lithium treatment ameliorates ketamine-induced mania-like behavior via the PI3K-AKT signaling pathway
Zoological Research November 18, 2022 Rongjun Ni, Tianhao Gao, Yi-Yan Wang et al.
Chronic lithium exposure reduces mania-like behavior and c-Fos expression in the medial prefrontal cortex of adult male mice treated with ketamine. Transcriptome sequencing of the prefrontal cortex shows that lithium inactivates the PI3K-AKT signaling pathway. Inhibiting AKT signaling with MK2206 or knocking down AKT in the mPFC reverses ketamine-induced mania, while activating AKT with SC79 promotes mania in low-dose ketamine-treated mice. Inhibiting PI3K with LY294002 also reverses mania, but inhibiting mTOR with rapamycin has no effect. Lithium may therefore ameliorate ketamine-induced mania via the PI3K-AKT pathway, suggesting a novel target for bipolar disorder treatment.