Antidepressant-like effects of medial prefrontal cortex deep brain stimulation in rats

Biol Psychiatry. 2010 Jan 15;67(2):117-24. doi: 10.1016/j.biopsych.2009.08.025.


Background: Subcallosal cingulate gyrus (SCG) deep brain stimulation (DBS) is being investigated as a treatment for major depression. We report on the effects of ventromedial prefrontal cortex (vmPFC) DBS in rats, focusing on possible mechanisms involved in an antidepressant-like response in the forced swim test (FST).

Methods: The outcome of vmPFC stimulation alone or combined with different types of lesions, including serotonin (5-HT) or norepineprhine (NE) depletion, was characterized in the FST. We also explored the effects of DBS on novelty-suppressed feeding, learned helplessness, and sucrose consumption in animals predisposed to helplessness.

Results: Stimulation at parameters approximating those used in clinical practice induced a significant antidepressant-like response in the FST. Ventromedial PFC lesions or local muscimol injections did not lead to a similar outcome. However, animals treated with vmPFC ibotenic acid lesions still responded to DBS, suggesting that the modulation of fiber near the electrodes could play a role in the antidepressant-like effects of stimulation. Also important was the integrity of the serotonergic system, as the effects of DBS in the FST were completely abolished in animals bearing 5-HT, but not NE, depleting lesions. In addition, vmPFC stimulation induced a sustained increase in hippocampal 5-HT levels. Preliminary work with other models showed that DBS was also able to influence specific aspects of depressive-like states in rodents, including anxiety and anhedonia, but not helplessness.

Conclusions: Our study suggests that vmPFC DBS in rats may be useful to investigate mechanisms involved in the antidepressant effects of SCG DBS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5,7-Dihydroxytryptamine / toxicity
  • Adrenergic Agents / toxicity
  • Analysis of Variance
  • Animals
  • Benzylamines / toxicity
  • Catheter Ablation / adverse effects
  • Deep Brain Stimulation / methods*
  • Depression / etiology
  • Depression / metabolism
  • Depression / physiopathology
  • Depression / therapy*
  • Disease Models, Animal
  • Excitatory Amino Acid Agonists / toxicity
  • Exploratory Behavior / physiology
  • Feeding Behavior / drug effects
  • Food Preferences / drug effects
  • GABA Agonists / toxicity
  • Helplessness, Learned
  • Ibotenic Acid / toxicity
  • Male
  • Microdialysis / methods
  • Muscimol / toxicity
  • Prefrontal Cortex / injuries
  • Prefrontal Cortex / physiology*
  • Raphe Nuclei / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin / metabolism
  • Serotonin Agents / toxicity
  • Swimming / physiology


  • Adrenergic Agents
  • Benzylamines
  • Excitatory Amino Acid Agonists
  • GABA Agonists
  • Serotonin Agents
  • Ibotenic Acid
  • Muscimol
  • 5,7-Dihydroxytryptamine
  • Serotonin
  • DSP 4