Behavioural Neurobiology Laboratory, Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, M5T 1R8, Canada.
Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada; Biopsychology Section, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, M5T 1R8, Canada.
Brain Stimul. 2018 Mar-Apr;11(2):423-425. doi: 10.1016/j.brs.2017.11.008. Epub 2017 Nov 15.
Some of the antidepressant-like effects of ventromedial prefrontal cortex (vmPFC) deep brain stimulation (DBS) in rodents have been attributed to the modulation of prefrontal-raphe pathways. This is largely different from selective serotonin reuptake inhibitors (SSRIs), which increase serotonin (5-HT) levels by inhibiting the serotonin transporter (SERT). SSRIs have limited efficacy when given to SERT knockout (KO) mice, or patients with mutations in the serotonin transporter promoter gene (5-HTTLPR).
vmPFC DBS will induce antidepressant-like effects and serotonin release in SERT KOs.
DBS-treated wild-type and SERT KO mice had a significant 22-26% decrease in immobility in the forced swim test. DBS delivered to either group was associated with 33-55% increase in 5-HT levels.
DBS induced a significant antidepressant-like effect in KO mice. This suggests that it may be reasonable to consider DBS in states where SERT is not fully operational.
一些腹内侧前额叶皮层（vmPFC）深部脑刺激（DBS）在啮齿动物中的抗抑郁样作用归因于前额叶-中缝核途径的调节。这与选择性 5-羟色胺再摄取抑制剂（SSRIs）有很大的不同，SSRIs 通过抑制 5-羟色胺转运蛋白（SERT）来增加 5-羟色胺（5-HT）水平。在 SERT 敲除（KO）小鼠或 5-羟色胺转运体启动子基因（5-HTTLPR）突变患者中给予 SSRIs 时，其疗效有限。
vmPFC DBS 将在 SERT KO 中诱导抗抑郁样效应和 5-HT 释放。
接受 DBS 治疗的野生型和 SERT KO 小鼠在强迫游泳试验中的不动时间减少了 22-26%。给予两组的 DBS 与 5-HT 水平增加 33-55%相关。
DBS 在 KO 小鼠中诱导了显著的抗抑郁样效应。这表明，在 SERT 不能完全发挥作用的情况下，考虑 DBS 可能是合理的。
