Abstract
Chronic ventromedial prefrontal cortex (vmPFC) deep brain stimulation (DBS) improves depressive-like behaviour in rats via serotonergic and neurotrophic-related mechanisms. We hypothesise that, in addition to these substrates, DBS-induced increases in hippocampal neurogenesis may also be involved. Our results show that stress-induced behavioural deficits in the sucrose preference test, forced swim test, novelty-suppressed feeding test (NSFT) and elevated plus maze were countered by chronic vmPFC DBS. In addition, stressed rats receiving stimulation had significant increases in hippocampal neurogenesis, PFC and hippocampal brain-derived neurotrophic factor levels. To block neurogenesis, stressed animals given DBS were injected with temozolomide. Such treatment reversed the anxiolytic-like effect of stimulation in the NSFT without significantly affecting performance in other behavioural tests. Taken together, our findings suggest that neuroplastic changes, including neurogenesis, may be involved in specific anxiolytic effects of DBS without affecting its general antidepressant-like response.
Highlights
The pathophysiology of depressive disorders is complex and not adequately understood
In a series of preclinical studies, we found that deep brain stimulation (DBS) delivered to the rodent homologue of the human subgenual cingulate region (that is, the ventromedial prefrontal cortex) induces antidepressant- and anti-anhedonic-like responses.[10,11,12,13,14]
The present results suggest that neuroplasticity-relevant changes, including neurogenesis and increases in brain-derived neurotrophic factor (BDNF), have a selective role in the beneficial effects of ventromedial prefrontal cortex (vmPFC) stimulation
Summary
The pathophysiology of depressive disorders is complex and not adequately understood. Subgenual cingulate region deep brain stimulation (DBS) is being investigated for the treatment of depression.[7,8,9] In a series of preclinical studies, we found that DBS delivered to the rodent homologue of the human subgenual cingulate region (that is, the ventromedial prefrontal cortex (vmPFC)) induces antidepressant- and anti-anhedonic-like responses.[10,11,12,13,14] The therapeutic mechanisms of this effect appear to be complex. Recent studies in rodents have shown that stimulation of limbic structures (for example, the entorhinal cortex and the anterior thalamic nucleus)[18,19,20,21] and the nucleus accumbens increases hippocampal neurogenesis.[22] To date, the effects of vmPFC DBS on neurogenesis have only been addressed in the context of memory.[23]
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