Deep brain stimulation induces antidepressant-like effects in serotonin transporter knockout mice

Publication date: Available online 15 November 2017
Source:Brain Stimulation
Author(s): Tatiana Bregman, Christina Nona, Julien Volle, Mustansir Diwan, Roger Raymond, Paul J. Fletcher, José N. Nobrega, Clement Hamani
BackgroundSome 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).HypothesisvmPFC DBS will induce antidepressant-like effects and serotonin release in SERT KOs.ResultsDBS-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.ConclusionsDBS 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.



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