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

ABSTRACT

BACKGROUND: 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). HYPOTHESIS: vmPFC DBS will induce antidepressant-like effects and serotonin release in SERT KOs. RESULTS: 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. CONCLUSIONS: 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.