Serotonin 5-HT receptors mediate the antidepressant- and anxiolytic-like effects of ventromedial prefrontal cortex deep brain stimulation in a mouse model of social defeat.

BACKGROUND

Deep brain stimulation (DBS) delivered to the ventromedial prefrontal cortex (vmPFC) induces antidepressant- and anxiolytic-like responses in various animal models. Electrophysiology and neurochemical studies suggest that these effects may be dependent, at least in part, on the serotonergic system. In rodents, vmPFC DBS reduces raphe cell firing and increases serotonin (5-HT) release and the expression of serotonergic receptors in different brain regions.

METHODS

We examined whether the behavioural responses of chronic vmPFC DBS are mediated by 5-HT or 5-HT receptors through a series of experiments. First, we delivered stimulation to mice undergoing chronic social defeat stress (CSDS), followed by a battery of behavioural tests. Second, we measured the expression of 5-HT and 5-HT receptors in different brain regions with western blot. Finally, we conducted pharmacological experiments to mitigate the behavioural effects of DBS using the 5-HT antagonist, WAY-100635, or the 5-HT antagonist, GR-127935.

RESULTS

We found that chronic DBS delivered to stressed animals reduced the latency to feed in the novelty suppressed feeding test (NSF) and immobility in the forced swim test (FST). Though no significant changes were observed in receptor expression, 5-HT levels in DBS-treated animals were found to be non-significantly increased in the vmPFC, hippocampus, and nucleus accumbens and reduced in the raphe compared to non-stimulated controls. Finally, while animals given vmPFC stimulation along with WAY-100635 still presented significant responses in the NSF and FST, these were mitigated following GR-127935 administration.

CONCLUSIONS

The antidepressant- and anxiolytic-like effects of DBS in rodents may be partially mediated by 5-HT1 receptors.