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

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

Background Paper

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• 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

5-HT (Serotonin)

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• Bred to be either SERT-/- or Sert+/+

• Undisclosed breed• 12 hr light/dark cycle– 7 am light cycle– Experiments started at 9 am

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The Rats

SERT-/- mice showed increased anxiety- and depression-like behavior

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The Takeaway

• Open Field Test (Fig 1)• Elevated Plus Maze (Fig 2)• Novelty Suppressed Feeding (Fig 3)• Home Cage Emergence Task (Fig 4)

Anxiety-Related Tests

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Open Field Test

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Elevated Plus Maze

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Novelty Suppressed Feeding

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Home Cage Emergence Task

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• Sucrose Consumption (Fig 5)– Sucrose Preference – Sucrose Intake

• Forced Swim Test (Fig 6)

Depression-Related Tests

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Sucrose Preference & Intake

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Forced Swim Test

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Microdialysis

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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

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

Selected Paper

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• 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

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Methods (The Rats)

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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

Surprise Background Paper

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