Lateral habenula deep brain stimulation alleviates depression-like behaviors and reverses the oscillatory pattern in the nucleus accumbens in an animal model of depression

Brain Res Bull. 2023 Oct 1:202:110745. doi: 10.1016/j.brainresbull.2023.110745. Epub 2023 Aug 19.

Abstract

Depression is a series of symptoms that influence mood, thinking, and behavior and create unpleasant emotions like hopelessness and apathy. Treatment-resistant depression (TRD) affects 30 % of depression patients despite the availability of several non-invasive therapies. Deep brain stimulation (DBS) is a novel therapy for TRD. The aim of the current study was to evaluate the effect of LHb-DBS by recording local field potentials (LFP) and conducting behavioral experiments. Thirty-two mature male Wistar rats were randomly divided into four groups: control, chronic mild stress (CMS), CMS+DBS, and DBS. After surgery and electrode placement in the lateral habenula (LHb), nucleus accumbens (NAc), and prelimbic cortex (PrL), the CMS protocol was applied for 3 weeks to create depression-like models. The open field test (OFT), sucrose preference test (SPT), and forced swim test (FST) were also performed. In the DBS groups, the LHb area was stimulated for four consecutive days. Finally, on the 22nd day, LFP was recorded from the NAc and PrL and analyzed using MATLAB software. Analyzing the findings using ANOVA and P-values ≤ 0.05 was considered. LHb-DBS alleviated depression-like behaviors in chronic moderate stress model rats (P ≤ 0.05). Three weeks of CMS enhanced almost all band powers in the NAc, while LHb-DBS decreased the power of the theta, alpha, beta, and gamma bands in the NAc (P ≤ 0.05), and the low-gamma band in the PrL. CMS also boosted the NAc-PrL coherence in low-frequency bands, while LHb-DBS increased beta and low gamma band coherence (P ≤ 0.05). In sum, the results of the present study showed that depression enhances low-frequency coherence between NAc and PrL cortex. Depression also potentiates many brain oscillations in the NAc, which can be mainly reversed by LHb-DBS.

Keywords: And local field potential; Depression; Lateral habenula; Nucleus accumbens; Prelimbic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Deep Brain Stimulation* / methods
  • Depression / therapy
  • Disease Models, Animal
  • Habenula* / physiology
  • Humans
  • Male
  • Nucleus Accumbens
  • Rats
  • Rats, Wistar