title: Prelimbic Stimulation Ameliorates Depressive-Like Behaviors and Increases Regional BDNF Expression in a Novel Drug-Resistant Animal Model of Depression.
abstract: BACKGROUND
  Approximately one third of all major depression patients fail to respond to conventional pharmacological antidepressants, and brain stimulation methods pose a promising alternative for this population. Recently, based on repeated multifactorial selective inbreeding of rats for depressive-like behaviors, we introduced a novel animal model for MDD. Rats from this Depressive Rat Line (DRL) exhibit inherent depressive-like behaviors, which are correlated with lower levels of brain-derived neurotrophic factor (BDNF) in specific brain regions. In addition, DRL rats do not respond to antidepressant medication but respond to electroconvulsive treatment, and they can thus be utilized to test the effectiveness of brain stimulation on hereditary, medication-resistant depressive-like behaviors.
  
  
  OBJECTIVE
  To test the effect of sub-convulsive electrical stimulation (SCES) of the prelimbic cortex, using TMS-like temporal pattern of stimulation, on depressive-like behaviors and regional BDNF levels in DRL rats.
  
  
  METHODS
  SCES sessions were administered daily for 10 days through chronically implanted electrodes. Temporal stimulation parameters were similar to those used in TMS for major depression in human patients. Depressive-like behaviors were assayed after treatment, followed by brain extraction and regional BDNF measurements.
  
  
  RESULTS
  SCES normalized both the depressive-like behaviors and the reduced BDNF levels observed in DRL rats. Correlation analyses suggest that changes in specific behaviors are mediated, at least in part, by BDNF expression in reward-related brain regions.
  
  
  CONCLUSIONS
  Brain stimulation is effective in a drug-resistant, inherited animal model for depression. BDNF alterations in specific regions may mediate different antidepressant effects.
authors.affiliation: Department of Life Sciences and the Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
authors.forename: Hagar
authors.initials: H
authors.lastname: Moshe
authors.affiliation: Department of Life Sciences and the Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
authors.forename: Ram
authors.initials: R
authors.lastname: Gal
authors.affiliation: Department of Life Sciences and the Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
authors.forename: Noam
authors.initials: N
authors.lastname: Barnea-Ygael
authors.affiliation: Department of Life Sciences and the Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Gulevsky
authors.affiliation: Department of Life Sciences and the Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
authors.forename: Uri
authors.initials: U
authors.lastname: Alyagon
authors.affiliation: Department of Life Sciences and the Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel. Electronic address: azangen@bgu.ac.il.
authors.forename: Abraham
authors.initials: A
authors.lastname: Zangen
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000235:genetics / Q000628:therapy*; D061218:Depressive Disorder, Treatment-Resistant / Q000188:drug therapy / Q000235:genetics / Q000628:therapy*; D004195:Disease Models, Animal; D004351:Drug Resistance / Q000187:drug effects; D004599:Electric Stimulation Therapy; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007178:Inbreeding; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward; D050781:Transcranial Magnetic Stimulation
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor
keywords: Animal model; Antidepressant; BDNF; Brain stimulation; Major depressive disorder; Prefrontal cortex