The majority of today’s antidepressants target the serotonin transporter (SERT). These drugs, however, are limited. SERT-targeted antidepressants not only take up to 4 weeks to take effect, but they may also have serious side effects, including suicide, and only a percentage of individuals who take them recover from depression following treatment. While ketamine has been considered as an alternative, its potentially addictive properties as well as the danger of schizophrenia have aroused concerns. As a result, there is a need for new, fast-acting antidepressant targets and compounds without these serious drawbacks. Here, Nan Sun and colleagues present one such solution. Sun and his team designed a fast-onset antidepressant that works by disrupting the interaction between SERT and neuronal nitric oxide synthase (nNOS). The authors found that disassociating SERT from nNOS in the brains of mice reduced intercellular serotonin in a brain region called the dorsal raphe nucleus. This enhanced serotonergic neuron activity in this area and dramatically increased serotonin release into the medial prefrontal cortex. According to the findings, this resulted in a fast-acting antidepressant effect in a mouse model of MDD. Reference: “Design of fast-onset antidepressant by dissociating SERT from nNOS in the DRN” by Nan Sun, Ya-Juan Qin, Chu Xu, Tian Xia, Zi-Wei Du, Li-Ping Zheng, An-an Li, Fan Meng, Yu Zhang, Jing Zhang, Xiao Liu, Ting-You Li, Dong-Ya Zhu and Qi-Gang Zhou, 27 October 2022, Science.DOI: 10.1126/science.abo3566
