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Feasibility and safety of continuous and chronic bilateral deep brain stimulation of the medial forebrain bundle in the naïve Sprague-Dawley rat.

Furlanetti LL, Döbrössy MD, Aranda IA, Coenen VA - Behav Neurol (2015)

Bottom Line: MFB-DBS led to increased and long-lasting c-fos expression in target regions of the mesolimbic/mesocortical system.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Stereotaxy and Interventional Neurosciences, Department of Stereotactic and Functional Neurosurgery, University Medical Center Freiburg, Breisacher Strasse 64, 79106 Freiburg, Germany.

ABSTRACT

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.

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Related in: MedlinePlus

Experimental groups and study design.
© Copyright Policy - open-access
Related In: Results  -  Collection


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fig1: Experimental groups and study design.

Mentions: Young adult female Sprague-Dawley (SD) rats (n = 16, Charles River, Germany), weighing 250 g, were housed in individual round cages (height: 40 cm; diameter: 40 cm), with the light/dark cycle maintained at 12 hours on and 12 hours off. Experimental groups and design are summarized in Figure 1. The study described in this paper had the approval of the Ethical Board of the University of Freiburg (Regierungspraesidium; TVA G10-124) and was carried out in accordance with the EU Directive 2010/63/EU concerning the protection of animals used for scientific purposes.


Feasibility and safety of continuous and chronic bilateral deep brain stimulation of the medial forebrain bundle in the naïve Sprague-Dawley rat.

Furlanetti LL, Döbrössy MD, Aranda IA, Coenen VA - Behav Neurol (2015)

Experimental groups and study design.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4414266&req=5

fig1: Experimental groups and study design.
Mentions: Young adult female Sprague-Dawley (SD) rats (n = 16, Charles River, Germany), weighing 250 g, were housed in individual round cages (height: 40 cm; diameter: 40 cm), with the light/dark cycle maintained at 12 hours on and 12 hours off. Experimental groups and design are summarized in Figure 1. The study described in this paper had the approval of the Ethical Board of the University of Freiburg (Regierungspraesidium; TVA G10-124) and was carried out in accordance with the EU Directive 2010/63/EU concerning the protection of animals used for scientific purposes.

Bottom Line: MFB-DBS led to increased and long-lasting c-fos expression in target regions of the mesolimbic/mesocortical system.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Stereotaxy and Interventional Neurosciences, Department of Stereotactic and Functional Neurosurgery, University Medical Center Freiburg, Breisacher Strasse 64, 79106 Freiburg, Germany.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus