3.5 D-serine has antidepressant-like effects through restraining the BDNF signaling pathway in the NAc
To determine the relationship between the antidepressant effect of D-serine and the BDNF system, K252a, a potent pharmacological inhibitor of the BDNF receptor TrkB was applied. C57BL/6J mice were premier daily infused with K252a (5 ug/perside, injected into the bilateral NAc) for 3 days, then treated with D-serine (5 ug/perside), and followed by the FST or TST. It was found that infusion of the K252a alone decreased the immobility of test mice in the FST and TST (Figure 5B and 5C). K252a pretreatment significantly facilitated the antidepressant effects of D-serine in the FST and TST. Furthermore, CSDS-stressed mice were co-treated with D-serine(5ug/perside) and K252a (5ug/perside) for 14 days, and behavioral tests were then implemented. Co-treatment K252a with D-serine significantly enhanced the antidepressant-like effects of D-serine in the sucrose preference test (Figure 5D) and social interaction test (Figure 5E). These results indicate that K252a enhances the antidepressant effects of D-serine.