Deep Brain Stimulation Reverses Anhedonic-Like Behavior in a Chronic Model of Depression: Role of Serotonin and Brain Derived Neurotrophic Factor

Deep Brain Stimulation Reverses Anhedonic-Like Behavior in a Chronic Model of Depression: Role of Serotonin and Brain Derived Neurotrophic Factor

Author Hamani, Clement Autor UNIFESP Google Scholar
Machado, Danilo C. Autor UNIFESP Google Scholar
Hipólide, Débora Cristina Autor UNIFESP Google Scholar
Dubiela, Francisco Paulino Autor UNIFESP Google Scholar
Suchecki, Deborah Autor UNIFESP Google Scholar
Macedo, Carlos E. Autor UNIFESP Google Scholar
Tescarollo, Fabio Autor UNIFESP Google Scholar
Martins, Uilton Autor UNIFESP Google Scholar
Covolan, Luciene Autor UNIFESP Google Scholar
Nobrega, Jose N. Google Scholar
Institution Ctr Addict & Mental Hlth
Toronto Western Hosp
Universidade Federal de São Paulo (UNIFESP)
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.
Keywords BDNF
cingulate gyrus
deep brain stimulation
prefrontal cortex
Language English
Sponsor National Alliance for Research on Schizophrenia and Depression
Ontario Mental Health Foundation
Canadian Institutes of Health Research
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Brazilian National Research Council
AFIP (Associacao Fundo de Incentivo a Pesquisa)
Date 2012-01-01
Published in Biological Psychiatry. New York: Elsevier B.V., v. 71, n. 1, p. 30-35, 2012.
ISSN 0006-3223 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 30-35
Access rights Closed access
Type Article
Web of Science ID WOS:000298137400008

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