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

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  1. Deep Brain Stimulation Reverses Anhedonic-Like Behavior in a Chronic Model of Depression: Role of Serotonin and Brain Derived Neurotrophic Factor Clement Hamani, Danilo C. Machado, Débora C. Hipólide, Francisco P. Dubiela, Deborah Suchecki, Carlos E. Macedo, Fabio Tescarollo, Uilton Martins, LucieneCovolan, and José N. Nobrega. Biol. Psychiatry 2012; 71:30-35

  2. Background Paper A Study in Male and Female 5-HT Transporter Knockout Rats: An Animal Model for Anxiety and Depression Disorders J. D. A. Olivier, M. G. C. Van der Hart, R. P. L. Van Swelm, P. J. Dederen, J. R. Homberg, T. Cremers, P. M. T. Deen, E. Cuppen, A. R. Cools and B. A. Ellenbroek Neuroscience 2008; 152:573-584

  3. 5-HT (Serotonin) • Key modulatory neurotransmitter • Used for treatment of anxiety and depression • Disturbances can result in depression • May result in permanent/long term effects • SERT (5-HTT) • 5-HT transporter • Responsible for reuptake by synaptic neuron prior to degradation/recycling

  4. The Rats • Bred to be either SERT-/- or Sert+/+ • Undisclosed breed • 12 hr light/dark cycle • 7 am light cycle • Experiments started at 9 am

  5. The Takeaway SERT-/- mice showed increased anxiety- and depression-like behavior

  6. Anxiety-Related Tests • Open Field Test (Fig 1) • Elevated Plus Maze (Fig 2) • Novelty Suppressed Feeding (Fig 3) • Home Cage Emergence Task (Fig 4)

  7. Open Field Test

  8. Elevated Plus Maze

  9. Novelty Suppressed Feeding

  10. Home Cage Emergence Task

  11. Depression-Related Tests • Sucrose Consumption (Fig 5) • Sucrose Preference • Sucrose Intake • Forced Swim Test (Fig 6)

  12. Sucrose Preference & Intake

  13. Forced Swim Test

  14. Microdialysis

  15. Selected Paper Deep Brain Stimulation Reverses Anhedonic-Like Behavior in a Chronic Model of Depression: Role of Serotonin and Brain Derived Neurotrophic Factor Clement Hamani, Danilo C. Machado, Débora C. Hipólide, Francisco P. Dubiela, Deborah Suchecki, Carlos E. Macedo, Fabio Tescarollo, Uilton Martins, Luciene Covolan, and José N. Nobrega. Biol. Psychiatry 2012; 71:30-35

  16. Methods (The Rats) • Wistar Rats • Light or Dark? • Controls • Injected with 0.1% ascorbic acid into the dorsal and median raphe nuclei • CUS & Non-CUS (chronic unpredictable mild stress) • Electrode & Sham Surgery • Test Subjects • Injected with 5,7-DHT into the dorsal and median raphe nuclei (Serotonin depletion) • CUS & Non-CUS • Electrode & Sham Surgery

  17. Surprise Background Paper Influence of BDNF and COMT polymorphisms on emotional decision making J. I. Kang, K. Namkoong, R. Y. Ha, K. Jhung, Y. T. Kim, and S. J. Kim Neuropharmacology 2010; 58:1109-1113

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