Site-Specific Antidepressant Effects of Repeated Subconvulsive Electrical Stimulation: Potential Role of Brain-Derived Neurotrophic Factor

doi:10.1016/j.biopsych.2009.09.015

Biological Psychiatry

Volume 67, Issue 2, 15 January 2010, Pages 125-132

https://doi.org/10.1016/j.biopsych.2009.09.015 Get rights and content

Background

Electroconvulsive therapy (ECT) is a very effective treatment for major depression. This method involves robust nonfocal stimulation of the brain and can normalize both neurochemical alterations and depressive behavior in animal models. We hypothesized that short stimulation sessions of specific reward-related brain sites might induce similar effects.

Methods

In the present study we compared behavioral and neurochemical effects produced by ECT and by repeated stimulation of reward-related brain sites, in a widely used rat model for depressive behavior induced by chronic mild stress (CMS). Different groups of rats received 10 sessions of either electroconvulsive shocks or subconvulsive electrical stimulation (SCES) of specific brain sites with an implanted electrode. The SCES temporal parameters were similar to those used in transcranial magnetic stimulation studies in humans. A battery of behavioral tests and measurements of brain-derived neurotrophic factor (BDNF) levels were used to assess the effectiveness of these treatments relative to sham treatments.

Results

Repeated SCES of either the nucleus accumbens (NAC) or the ventral but not the dorsal prelimbic cortex (PLC) reversed the main behavioral deficit and the reduction of BDNF levels in the hippocampus that were induced by CMS. The ECT was more effective because it also normalized a behavioral deficit associated with anxiety but produced a learning and memory impairment.

Conclusions

This study implicates the ventral PLC and the NAC in the pathophysiology of depressive behavior and suggests that local intermittent SCES can induce an antidepressant effect similar to that of ECT, without the cognitive impairment caused by the convulsive treatment.

Section snippets

Experimental Design

The experimental design is represented in Figure 1. Animals intended for the SCES experiments (real or sham) underwent surgery to implant electrodes before the initiation of the CMS protocol. After completion of the 4-week CMS protocol, either ECT or SCES treatment (active or sham; n = 10–14/group) was performed for 10 days. Subsequently, animals underwent behavioral tests during a 3-week period in the following sequence: sucrose preference, home-cage locomotion, exploration, forced swim test,

Sucrose Preference

The CMS induced significant reductions in sucrose preference relative to the control groups (Figure 2), as described previously (19). A comparison between sucrose preference scores, measured in the ECT experimental groups revealed a significant group effect [F(2,38) = 5.28, p = .0062; Figure 2A). Post hoc analysis showed that sucrose preference was significantly decreased in sham-treated CMS animals relative to non-CMS control subjects, whereas ECT significantly increased sucrose preference in

Discussion

Electroconvulsive therapy is a very effective antidepressant treatment but incorporates major drawbacks, such as the need for general anesthesia, and an accompanied generalized seizure, resulting in undesirable cognitive side-effects. In this study we found that repeated subconvulsive localized stimulation of reward-related brain sites can induce comparable antidepressant and neurochemical effects in an animal model. The impaired sucrose preference induced by CMS, which is considered a measure

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In contrast, apart from a few studies (Angelucci et al., 2003; Gao et al., 2016; Kronenberg et al., 2018), BDNF was found to increase in the hippocampus of chronically stressed rats from hours to days after repeated ECS (Luo et al., 2012, 2015; Kyeremanteng et al., 2014; O'Donovan et al., 2014; Zhang et al., 2016). Increased BDNF levels are more robust in the dorsal hippocampus (Gersner et al., 2014) than in the ventral hippocampus (Gersner et al., 2010). Moreover, repeated ECS treatment could normalize both the depressive-like behavioral impairments and BDNF-related molecular alterations in “depressed” rat lines for more than 2 months (Gersner et al., 2014); however this was not found in the study by Kronenberg et al. (2018).
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: Drs. Gersner and Toth contributed equally to this study.

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Archival ReportSite-Specific Antidepressant Effects of Repeated Subconvulsive Electrical Stimulation: Potential Role of Brain-Derived Neurotrophic Factor

Background

Methods

Results

Conclusions

Section snippets

Experimental Design

Sucrose Preference

Discussion

Psychiatr Clin North Am

J Affect Disord

Biol Psychiatry

Clin Neurophysiol

Clin Neurophysiol

Brain Stimulat

Neuron

Biol Psychiatry

Biol Psychiatry

Neurosci Biobehav Rev

Neurosci Biobehav Rev

Physiol Behav

Eur Psychiatry

Biol Psychiatry

Biol Psychiatry

Biol Psychiatry

J Neurosci Methods

J Neurosci Methods

Neuroscience

Neuroscience

Neuroscience

Prog Neurobiol

Neuroscience

Psychiatry Res

Biol Psychiatry

Pharmacol Ther

Med Hypotheses

Prog Neuropsychopharmacol Biol Psychiatry

The epidemiology of major depressive disorder: Results from the national comorbidity Survey replication (NCS-R)

JAMA

Efficacy of ECT in depression: A meta-analytic review

J ECT

Subtypes of memory dysfunction associated with ECT: Characteristics and neurobiological bases

J ECT

Archival Report
Site-Specific Antidepressant Effects of Repeated Subconvulsive Electrical Stimulation: Potential Role of Brain-Derived Neurotrophic Factor