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Deep brain stimulation induces antidepressant-like effects in serotonin transporter knockout mice
Tatiana Bregman1, Christina Nona1, Julien Volle1
1Behavioural Neurobiology Laboratory, Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, M5T 1R8, Canada.
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.
