Elsevier

Biological Psychiatry

Volume 67, Issue 2, 15 January 2010, Pages 117-124
Biological Psychiatry

Archival Report
Antidepressant-Like Effects of Medial Prefrontal Cortex Deep Brain Stimulation in Rats

https://doi.org/10.1016/j.biopsych.2009.08.025Get rights and content

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.

Section snippets

Methods and Materials

All protocols were approved by the Animal Care committee of the Centre for Addiction and Mental Health.

Outcome of vmPFC DBS in the FST

Animals treated with vmPFC DBS (n = 13) showed a 45% decrease in immobility scores compared with control animals (n = 12; p = .004; Figure 1B). A similar antidepressant-like response was not observed after striatal stimulation (n = 6; Figure 1C), suggesting that the effects of DBS had some target specificity. As a positive control, imipramine-treated rats (n = 8) had a 55% reduction in immobility scores (p = .002; Figure 1D), a magnitude of response similar to that in the DBS group.

To rule out

Discussion

We found that vmPFC DBS induced a clear antidepressant-like response in the FST, a well-established paradigm to assess antidepressant activity in rodents (16, 17, 18, 19, 20). In addition to different classes of medications, interventions such as electroconvulsive therapy and vagus nerve stimulation have all shown antidepressant-like effects in this model (16, 17, 18, 19, 20, 21, 24, 34). While the predictive validity of the FST is strong, a common criticism to its face validity refers to the

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