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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

Behavioral testing. MFB-HFS did not have any specific effects on the animals' anxiolytic behavior as measured by the elevated plus maze: stimulated animals performed identical to the controls both before and after stimulation (a). Similarly, the stimulation had no impact on the animals' performance in the Forced Swim Test, a measure of behavioral despair (b). See text for more detail. ∗P < 0.05 closed arm compared to open arm.
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fig6: Behavioral testing. MFB-HFS did not have any specific effects on the animals' anxiolytic behavior as measured by the elevated plus maze: stimulated animals performed identical to the controls both before and after stimulation (a). Similarly, the stimulation had no impact on the animals' performance in the Forced Swim Test, a measure of behavioral despair (b). See text for more detail. ∗P < 0.05 closed arm compared to open arm.

Mentions: Tests confirmed that the chronic MFB-HFS did not induce any behavioral abnormalities in the animals. Changes in the anxiolytic behavior were measured using the elevated plus maze before and after stimulation in the control and experimental animals. The data shows that all tested animals spent similar percentage of the time in the “closed arm” and that this proportion increased in a similar fashion across the groups between the two testing sessions (Figure 6(a), Group × Session F(1,12) = 0.72, n.s.). Similarly, performance on the Forced Swim Test, measuring behavioral despair, was not affected by chronic and continuous MFB-HFS (Figure 6(b), Group × Session, F(1,13) = 0.18, n.s.).


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)

Behavioral testing. MFB-HFS did not have any specific effects on the animals' anxiolytic behavior as measured by the elevated plus maze: stimulated animals performed identical to the controls both before and after stimulation (a). Similarly, the stimulation had no impact on the animals' performance in the Forced Swim Test, a measure of behavioral despair (b). See text for more detail. ∗P < 0.05 closed arm compared to open arm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig6: Behavioral testing. MFB-HFS did not have any specific effects on the animals' anxiolytic behavior as measured by the elevated plus maze: stimulated animals performed identical to the controls both before and after stimulation (a). Similarly, the stimulation had no impact on the animals' performance in the Forced Swim Test, a measure of behavioral despair (b). See text for more detail. ∗P < 0.05 closed arm compared to open arm.
Mentions: Tests confirmed that the chronic MFB-HFS did not induce any behavioral abnormalities in the animals. Changes in the anxiolytic behavior were measured using the elevated plus maze before and after stimulation in the control and experimental animals. The data shows that all tested animals spent similar percentage of the time in the “closed arm” and that this proportion increased in a similar fashion across the groups between the two testing sessions (Figure 6(a), Group × Session F(1,12) = 0.72, n.s.). Similarly, performance on the Forced Swim Test, measuring behavioral despair, was not affected by chronic and continuous MFB-HFS (Figure 6(b), Group × Session, F(1,13) = 0.18, n.s.).

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