title: Medial Forebrain Bundle Deep Brain Stimulation has Symptom-specific Anti-depressant Effects in Rats and as Opposed to Ventromedial Prefrontal Cortex Stimulation Interacts With the Reward System.
abstract: BACKGROUND
  In recent years, deep brain stimulation (DBS) has emerged as a promising treatment option for patients suffering from treatment-resistant depression (TRD). Several stimulation targets have successfully been tested in clinical settings, including the subgenual cingulum (Cg25) and the medial forebrain bundle (MFB). MFB-DBS has led to remarkable results, surpassing the effect of previous targets in terms of response latency and number of responders. However, the question remains as to which mechanisms underlie this difference.
  
  
  OBJECTIVE
  The aim of the present study was to thoroughly study the anti-depressant effect of MFB-DBS in the Flinders sensitive line (FSL) rat model of depression as well as to investigate whether MFB-DBS and Cg25-DBS operate through the same neurobiological circuits.
  
  
  METHODS
  FSL and control rats received bilateral high-frequency stimulation to the MFB at the level of the lateral hypothalamus, while being subjected to a variety of depression- and anxiety-related behavioral paradigms. To further compare the effects of MFB-DBS and Cg25-DBS on reward-related behavior, animals were stimulated in either the MFB or ventromedial prefrontal cortex (vmPFC, rodent analog to Cg25), while being tested in the intra-cranial self-stimulation paradigm.
  
  
  RESULTS
  A marked symptom-specific anti-depressant effect of MFB-DBS was demonstrated. The ICSS-paradigm revealed that MFB-DBS, as opposed to vmPFC-DBS interacts with the reward system.
  
  
  CONCLUSIONS
  Our data suggest that MFB-DBS and Cg25-DBS do not operate via the same neurobiological circuits. This differentiation might be of interest when selecting patients for either Cg25- or MFB-DBS.
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; International Graduate Program Medical Neurosciences, Charité Universitätsmedizin Berlin, Germany.
authors.forename: Henriette
authors.initials: H
authors.lastname: Edemann-Callesen
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; International Graduate Program Medical Neurosciences, Charité Universitätsmedizin Berlin, Germany.
authors.forename: Mareike
authors.initials: M
authors.lastname: Voget
authors.affiliation: International Graduate Program Medical Neurosciences, Charité Universitätsmedizin Berlin, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Empl
authors.affiliation: Master Program Life Sciences and Technology, École Polytechnique Fédérale de Lausanne, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Vogel
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Wieske
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; International Graduate Program Medical Neurosciences, Charité Universitätsmedizin Berlin, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Rummel
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Heinz
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Aleksander A
authors.initials: AA
authors.lastname: Mathé
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.
authors.forename: Ravit
authors.initials: R
authors.lastname: Hadar
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany. Electronic address: christine.winter@uniklinikum-dresden.de.
authors.forename: Christine
authors.initials: C
authors.lastname: Winter
mesh_terms: D000818:Animals; D046690:Deep Brain Stimulation; D003863:Depression / Q000628:therapy; D008297:Male; D008474:Medial Forebrain Bundle / Q000502:physiology*; D017397:Prefrontal Cortex / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012201:Reward; D012653:Self Stimulation / Q000502:physiology*
keywords: Deep brain stimulation; Flinders sensitive rats; Intra-cranial self-stimulation; Medial forebrain bundle; Reward system; Treatment resistant depression