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

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 se...

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Published in:	Biological psychiatry (1969) Vol. 71; no. 1; pp. 30 - 35
Main Authors:	Hamani, Clement, Machado, Danilo C, Hipólide, Débora C, Dubiela, Francisco P, Suchecki, Deborah, Macedo, Carlos E, Tescarollo, Fabio, Martins, Uilton, Covolan, Luciene, Nobrega, José N
Format:	Journal Article
Language:	English
Published:	New York, NY Elsevier Inc 01-01-2012 Elsevier
Subjects:	5,7-Dihydroxytryptamine - toxicity Adult and adolescent clinical studies Animals BDNF Biological and medical sciences Brain-Derived Neurotrophic Factor - metabolism cingulate gyrus deep brain stimulation Deep Brain Stimulation - methods Depression Depression - physiopathology Depression - therapy Disease Models, Animal Electrodes, Implanted Gene Expression Regulation Male Medical sciences Mood disorders prefrontal cortex Prefrontal Cortex - physiology Psychiatry Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Rats Rats, Wistar serotonin Serotonin - metabolism Serotonin Agents - toxicity Sucrose - administration & dosage Time Factors Water Deprivation serotonin BDNF prefrontal cortex depression psychiatry cingulate gyrus deep brain stimulation Mood disorder Affect affectivity Serotonin Deep brain stimulation Central nervous system Anhedonia Depression Prefrontal cortex Encephalon Chronic Treatment Cingulate cortex Neurotransmitter Models Behavior Brain derived neurotrophic factor Psychiatry
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Summary:	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.
ISSN:	0006-3223 1873-2402
DOI:	10.1016/j.biopsych.2011.08.025