Feasibility and Safety of Continuous and Chronic Bilateral Deep Brain Stimulation of the Medial Forebrain Bundle in the Naïve Sprague-Dawley Rat

Objective. Deep brain stimulation (DBS) of the superolateral branch of the medial forebrain bundle (MFB) has provided rapid and dramatic reduction of depressive symptoms in a clinical trial. Early intracranial self-stimulation experiments of the MFB suggested detrimental side effects on the animals’...

Full description

Saved in:
Bibliographic Details
Main Authors: Luciano L. Furlanetti, Máté D. Döbrössy, Iñigo A. Aranda, Volker A. Coenen
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:Behavioural Neurology
Online Access:http://dx.doi.org/10.1155/2015/256196
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832551799750393856
author Luciano L. Furlanetti
Máté D. Döbrössy
Iñigo A. Aranda
Volker A. Coenen
author_facet Luciano L. Furlanetti
Máté D. Döbrössy
Iñigo A. Aranda
Volker A. Coenen
author_sort Luciano L. Furlanetti
collection DOAJ
description Objective. Deep brain stimulation (DBS) of the superolateral branch of the medial forebrain bundle (MFB) has provided rapid and dramatic reduction of depressive symptoms in a clinical trial. Early intracranial self-stimulation experiments of the MFB suggested detrimental side effects on the animals’ health; therefore, the current study looked at the viability of chronic and continuous MFB-DBS in rodents, with particular attention given to welfare issues and identification of stimulated pathways. Methods. Sprague-Dawley female rats were submitted to stereotactic microelectrode implantation into the MFB. Chronic continuous DBS was applied for 3–6 weeks. Welfare monitoring and behavior changes were assessed. Postmortem histological analysis of c-fos protein expression was carried out. Results. MFB-DBS resulted in mild and temporary weight loss in the animals, which was regained even with continuing stimulation. MFB-DBS led to increased and long-lasting c-fos expression in target regions of the mesolimbic/mesocortical system. Conclusions. Bilateral continuous chronic MFB-DBS is feasible, safe, and without impact on the rodent’s health. MFB-DBS results in temporary increase in exploration, which could explain the initial weight loss, and does not produce any apparent behavioral abnormalities. This platform represents a powerful tool for further preclinical investigation of the MFB stimulation in the treatment of depression.
format Article
id doaj-art-541894f793f14234898d11833d266d05
institution Kabale University
issn 0953-4180
1875-8584
language English
publishDate 2015-01-01
publisher Wiley
record_format Article
series Behavioural Neurology
spelling doaj-art-541894f793f14234898d11833d266d052025-02-03T06:00:23ZengWileyBehavioural Neurology0953-41801875-85842015-01-01201510.1155/2015/256196256196Feasibility and Safety of Continuous and Chronic Bilateral Deep Brain Stimulation of the Medial Forebrain Bundle in the Naïve Sprague-Dawley RatLuciano L. Furlanetti0Máté D. Döbrössy1Iñigo A. Aranda2Volker A. Coenen3 Laboratory of Stereotaxy and Interventional Neurosciences, Department of Stereotactic and Functional Neurosurgery, University Medical Center Freiburg, Breisacher Strasse 64, 79106 Freiburg, Germany Laboratory of Stereotaxy and Interventional Neurosciences, Department of Stereotactic and Functional Neurosurgery, University Medical Center Freiburg, Breisacher Strasse 64, 79106 Freiburg, Germany Laboratory of Stereotaxy and Interventional Neurosciences, Department of Stereotactic and Functional Neurosurgery, University Medical Center Freiburg, Breisacher Strasse 64, 79106 Freiburg, Germany Laboratory of Stereotaxy and Interventional Neurosciences, Department of Stereotactic and Functional Neurosurgery, University Medical Center Freiburg, Breisacher Strasse 64, 79106 Freiburg, GermanyObjective. Deep brain stimulation (DBS) of the superolateral branch of the medial forebrain bundle (MFB) has provided rapid and dramatic reduction of depressive symptoms in a clinical trial. Early intracranial self-stimulation experiments of the MFB suggested detrimental side effects on the animals’ health; therefore, the current study looked at the viability of chronic and continuous MFB-DBS in rodents, with particular attention given to welfare issues and identification of stimulated pathways. Methods. Sprague-Dawley female rats were submitted to stereotactic microelectrode implantation into the MFB. Chronic continuous DBS was applied for 3–6 weeks. Welfare monitoring and behavior changes were assessed. Postmortem histological analysis of c-fos protein expression was carried out. Results. MFB-DBS resulted in mild and temporary weight loss in the animals, which was regained even with continuing stimulation. MFB-DBS led to increased and long-lasting c-fos expression in target regions of the mesolimbic/mesocortical system. Conclusions. Bilateral continuous chronic MFB-DBS is feasible, safe, and without impact on the rodent’s health. MFB-DBS results in temporary increase in exploration, which could explain the initial weight loss, and does not produce any apparent behavioral abnormalities. This platform represents a powerful tool for further preclinical investigation of the MFB stimulation in the treatment of depression.http://dx.doi.org/10.1155/2015/256196
spellingShingle Luciano L. Furlanetti
Máté D. Döbrössy
Iñigo A. Aranda
Volker A. Coenen
Feasibility and Safety of Continuous and Chronic Bilateral Deep Brain Stimulation of the Medial Forebrain Bundle in the Naïve Sprague-Dawley Rat
Behavioural Neurology
title Feasibility and Safety of Continuous and Chronic Bilateral Deep Brain Stimulation of the Medial Forebrain Bundle in the Naïve Sprague-Dawley Rat
title_full Feasibility and Safety of Continuous and Chronic Bilateral Deep Brain Stimulation of the Medial Forebrain Bundle in the Naïve Sprague-Dawley Rat
title_fullStr Feasibility and Safety of Continuous and Chronic Bilateral Deep Brain Stimulation of the Medial Forebrain Bundle in the Naïve Sprague-Dawley Rat
title_full_unstemmed Feasibility and Safety of Continuous and Chronic Bilateral Deep Brain Stimulation of the Medial Forebrain Bundle in the Naïve Sprague-Dawley Rat
title_short Feasibility and Safety of Continuous and Chronic Bilateral Deep Brain Stimulation of the Medial Forebrain Bundle in the Naïve Sprague-Dawley Rat
title_sort feasibility and safety of continuous and chronic bilateral deep brain stimulation of the medial forebrain bundle in the naive sprague dawley rat
url http://dx.doi.org/10.1155/2015/256196
work_keys_str_mv AT lucianolfurlanetti feasibilityandsafetyofcontinuousandchronicbilateraldeepbrainstimulationofthemedialforebrainbundleinthenaivespraguedawleyrat
AT mateddobrossy feasibilityandsafetyofcontinuousandchronicbilateraldeepbrainstimulationofthemedialforebrainbundleinthenaivespraguedawleyrat
AT inigoaaranda feasibilityandsafetyofcontinuousandchronicbilateraldeepbrainstimulationofthemedialforebrainbundleinthenaivespraguedawleyrat
AT volkeracoenen feasibilityandsafetyofcontinuousandchronicbilateraldeepbrainstimulationofthemedialforebrainbundleinthenaivespraguedawleyrat