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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

Liquid consumption. As in indicator of welfare, liquid consumption over a 24-hour period was periodically monitored during the study. The animals' consumption of neither water (a) nor 10% sucrose (b) was influenced by MFB-HFS during the study period.
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fig4: Liquid consumption. As in indicator of welfare, liquid consumption over a 24-hour period was periodically monitored during the study. The animals' consumption of neither water (a) nor 10% sucrose (b) was influenced by MFB-HFS during the study period.

Mentions: There was no overall difference across the groups in their average daily dry food consumption (Figure 3(a), Group F(3,12) = 0.9, n.s.), but when analyzed over time, animals receiving MFB-HFS reduced their intake by about 25% for up to 20 days (Group × Time, F(18,72) = 2.93, P < 0.001), which also explains the temporary stimulation induced weight loss. Similarly, overall across the study there were no group differences in feces production (Figure 3(b), group, F(3,12) = 1.79, n.s.). However, up to 6 days of stimulation, DBS B showed a tendency and DBS C a significant reduction of about 25% in feces production (Group × Time, F(24,96) = 3.08, P < 0.001). Importantly when considering welfare issues MFB-HFS did not have an impact on either water consumption (Figure 4(a), Group × Time F(10,140) = 0.75, n.s.) or 10% sucrose consumption throughout the period of the study nor during the stimulation phases (Figure 4(b), Group × Time F(9,126) = 1.40, 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)

Liquid consumption. As in indicator of welfare, liquid consumption over a 24-hour period was periodically monitored during the study. The animals' consumption of neither water (a) nor 10% sucrose (b) was influenced by MFB-HFS during the study period.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig4: Liquid consumption. As in indicator of welfare, liquid consumption over a 24-hour period was periodically monitored during the study. The animals' consumption of neither water (a) nor 10% sucrose (b) was influenced by MFB-HFS during the study period.
Mentions: There was no overall difference across the groups in their average daily dry food consumption (Figure 3(a), Group F(3,12) = 0.9, n.s.), but when analyzed over time, animals receiving MFB-HFS reduced their intake by about 25% for up to 20 days (Group × Time, F(18,72) = 2.93, P < 0.001), which also explains the temporary stimulation induced weight loss. Similarly, overall across the study there were no group differences in feces production (Figure 3(b), group, F(3,12) = 1.79, n.s.). However, up to 6 days of stimulation, DBS B showed a tendency and DBS C a significant reduction of about 25% in feces production (Group × Time, F(24,96) = 3.08, P < 0.001). Importantly when considering welfare issues MFB-HFS did not have an impact on either water consumption (Figure 4(a), Group × Time F(10,140) = 0.75, n.s.) or 10% sucrose consumption throughout the period of the study nor during the stimulation phases (Figure 4(b), Group × Time F(9,126) = 1.40, 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