title: Deep brain stimulation reverses anhedonic-like behavior in a chronic model of depression: role of serotonin and brain derived neurotrophic factor.
abstract: BACKGROUND
  Deep brain stimulation (DBS) is being investigated as a treatment for major depression, but its mechanisms of action are still unknown. We have studied the effects of ventromedial prefrontal cortex (vmPFC) stimulation in a chronic model of depression and assessed the involvement of the serotonergic system and brain derived neurotrophic factor (BDNF) in a DBS response.
  
  
  METHODS
  Rats were subjected to chronic unpredictable mild stress during 4 weeks. Decline in preference for sucrose solutions over water, an index suggested to reflect anhedonic-like behavior, was monitored on a weekly basis. The outcome of chronic vmPFC stimulation alone (8 hours/day for 2 weeks) or combined with serotonin-depleting lesions was characterized. BDNF levels were measured in the hippocampus.
  
  
  RESULTS
  Stress induced a significant decrease in sucrose preference as well as hippocampal BDNF levels as compared with those recorded in control subjects. vmPFC stimulation completely reversed this behavioral deficit and partially increased BDNF levels. In contrast, DBS did not improve stress-induced anhedonic-like behavior in animals bearing serotonin-depleting raphe lesions with associated normal hippocampal BDNF levels.
  
  
  CONCLUSIONS
  vmPFC stimulation was effective in a chronic model of depression. Our results suggest that the integrity of the serotonergic system is important for the anti-anhedonic-like effects of DBS but question a direct role of hippocampal BDNF.
authors: Neuroimaging Research Section, Centre for Addiction and Mental Health, Toronto Western Hospital, 250 College Street, Toronto, Ontario, Canada. Clement.Hamani@uhn.on.ca
authors: Clement
authors: C
authors: Hamani
authors: Danilo C
authors: DC
authors: Machado
authors: Débora C
authors: DC
authors: Hipólide
authors: Francisco P
authors: FP
authors: Dubiela
authors: Deborah
authors: D
authors: Suchecki
authors: Carlos E
authors: CE
authors: Macedo
authors: Fabio
authors: F
authors: Tescarollo
authors: Uilton
authors: U
authors: Martins
authors: Luciene
authors: L
authors: Covolan
authors: José N
authors: JN
authors: Nobrega
mesh_terms: D015116:5,7-Dihydroxytryptamine / Q000633:toxicity; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D046690:Deep Brain Stimulation / Q000379:methods*; D003863:Depression / Q000503:physiopathology* / Q000628:therapy*; D004195:Disease Models, Animal; D004567:Electrodes, Implanted; D005786:Gene Expression Regulation; D008297:Male; D017397:Prefrontal Cortex / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000633:toxicity; D013395:Sucrose / Q000008:administration & dosage; D013997:Time Factors; D014868:Water Deprivation
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018490:Serotonin Agents; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D013395:Sucrose