Chronic deep brain stimulation of the lateral habenula nucleus in a rat model of depression

Abstract

In the present study, we aim to determine the antidepressant effects of chronic deep brain stimulation (DBS) of the lateral habenula nucleus (LHb) in a rat model of depression and to explore the potential mechanism of DBS induced improvement of depressive symptoms. To establish the rat depression model, animals were repeatedly exposed to a set of chronic mild stressors for four consecutive weeks. The open-field and sucrose consumption tests were used as measures of depression. For DBS treatment, rats were stereotaxically implanted with electrodes into the LHb and stimulated over a course of 28 d. A separate positive control group was given pharmacotherapy with clomipramine hydrochloride. Open-field testing was used to determine behavioral changes following DBS treatment. Monoamine concentrations in blood and brain tissues were determined by fluorescence spectrophotometry. This study demonstrates that DBS of the LHb region significantly improved depressive-like symptoms in the rat model. These improvements manifested as elevated numbers of crossings and rearings during the open-field test in DBS-treated depressed rats compared to controls. In addition, concentrations of monoamines including norepinephrine (NE), dopamine (DA), and serotonin (5-HT) in blood serum and brain tissues were also increased by DBS of the LHb. Therefore, significant improvements in all outcomes were detected following chronic DBS treatment. These results indicate that long-term DBS treatment of the LHb region effectively improved depressive symptoms in rats, likely as a result of elevated monoamine levels. LHb DBS may therefore provide a valuable therapeutic strategy for the clinical treatment of depression.