AI Article Synopsis
- The study investigates the effects of deep brain stimulation (DBS) on the superolateral-branch of the medial forebrain bundle (MFB) as a potential treatment for treatment-resistant depression (TRD) in rats.
- Male Wistar rats were divided into three groups (sham-operated, DBS-Off, and DBS-On) to assess the behavioral and chemical changes linked to reward processing in the brain.
- Results showed that MFB-DBS significantly increased antidepressant-like behaviors and boosted levels of specific dopamine receptors and transporters in key brain regions but did not alter other dopamine system markers, indicating its potential therapeutic role.
Article Abstract
Background: Among several potential neuroanatomical targets pursued for deep brain stimulation (DBS) for treating those with treatment-resistant depression (TRD), the superolateral-branch of the medial forebrain bundle (MFB) is emerging as a privileged location. We investigated the antidepressant-like phenotypic and chemical changes associated with reward-processing dopaminergic systems in rat brains after MFB-DBS.
Methods: Male Wistar rats were divided into three groups: sham-operated, DBS-Off, and DBS-On. For DBS, a concentric bipolar electrode was stereotactically implanted into the right MFB. Exploratory activity and depression-like behavior were evaluated using the open-field and forced-swimming test (FST), respectively. MFB-DBS effects on the dopaminergic system were evaluated using immunoblotting for tyrosine hydroxylase (TH), dopamine transporter (DAT), and dopamine receptors (D1-D5), and high-performance liquid chromatography for quantifying dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in brain homogenates of prefrontal cortex (PFC), hippocampus, amygdala, and nucleus accumbens (NAc).
Results: Animals receiving MFB-DBS showed a significant increase in swimming time without alterations in locomotor activity, relative to the DBS-Off (p<0.039) and sham-operated groups (p<0.014), indicating an antidepressant-like response. MFB-DBS led to a striking increase in protein levels of dopamine D2 receptors and DAT in the PFC and hippocampus, respectively. However, we did not observe appreciable differences in the expression of other dopamine receptors, TH, or in the concentrations of dopamine, DOPAC, and HVA in PFC, hippocampus, amygdala, and NAc.
Limitations: This study was not performed on an animal model of TRD.
Conclusion: MFB-DBS rescues the depression-like phenotypes and selectively activates expression of dopamine receptors in brain regions distant from the target area of stimulation.
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| http://dx.doi.org/10.1016/j.jad.2017.03.074 | DOI Listing |
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