title: Feasibility and safety of continuous and chronic bilateral deep brain stimulation of the medial forebrain bundle in the naïve Sprague-Dawley rat.
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.
authors.affiliation: Laboratory of Stereotaxy and Interventional Neurosciences, Department of Stereotactic and Functional Neurosurgery, University Medical Center Freiburg, Breisacher Strasse 64, 79106 Freiburg, Germany.
authors.forename: Luciano L
authors.initials: LL
authors.lastname: Furlanetti
authors.affiliation: Laboratory of Stereotaxy and Interventional Neurosciences, Department of Stereotactic and Functional Neurosurgery, University Medical Center Freiburg, Breisacher Strasse 64, 79106 Freiburg, Germany.
authors.forename: Máté D
authors.initials: MD
authors.lastname: Döbrössy
authors.affiliation: Laboratory of Stereotaxy and Interventional Neurosciences, Department of Stereotactic and Functional Neurosurgery, University Medical Center Freiburg, Breisacher Strasse 64, 79106 Freiburg, Germany.
authors.forename: Iñigo A
authors.initials: IA
authors.lastname: Aranda
authors.affiliation: Laboratory of Stereotaxy and Interventional Neurosciences, Department of Stereotactic and Functional Neurosurgery, University Medical Center Freiburg, Breisacher Strasse 64, 79106 Freiburg, Germany.
authors.forename: Volker A
authors.initials: VA
authors.lastname: Coenen
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D046690:Deep Brain Stimulation / Q000379:methods; D003863:Depression / Q000503:physiopathology*; D004298:Dopamine / Q000378:metabolism; D004558:Electric Stimulation / Q000379:methods; D005240:Feasibility Studies; D005260:Female; D008474:Medial Forebrain Bundle / Q000601:surgery*; D017207:Rats, Sprague-Dawley
chemical_list: D004298:Dopamine