Electrical high frequency stimulation of the nucleus accumbens shell does not modulate depressive-like behavior in rats

Deep brain stimulation (DBS) is an effective tool for treatment-resistant depression, though it is still unclear which brain area to target in order to get robust results. While research suggests that the nucleus accumbens (NAc) plays an important role in depression, studies using NAc DBS to improve depressive behavior have not been able to fully explain underlying molecular mechanisms. We therefore used unilateral high frequency stimulation of the NAc shell in rats to verify its effectiveness in treating depression and study involved neurotransmitter systems. Animals underwent social isolation and food deprivation to induce depressive-like symptoms, and performed the forced swim test (FST) to see possible changes in depressive behavior due to NAc shell stimulation. Neurotransmitter levels were measured using in-vivo microdialysis to detect DBS-induced changes. Non-treated control rats showed no significant difference between swimming and floating during FST, verifying that our depression model induced depressive-like symptoms in rats. Furthermore, stimulated and sham-operated animals showed a significant increase in mobility during FST compared to control rats, suggesting an improvement of depressive-like symptoms. However, stimulated rats did not differ from sham-operated rats in their behavior during FST, nor did neurotransmitter levels significantly changed in stimulated rats compared to control rats. Our data suggest that NAc shell stimulation did not alter depressive behavior in rats and had no effects on the molecular level. However, depressive behavior was positively altered when stimulation electrode and microdialysis probe were inserted simultaneously into the NAc shell, causing significant tissue damage and therefore possibly altering the glutamatergic system.