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

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

Author information

1
Neuroimaging Research Section, Centre for Addiction and Mental Health, Toronto, Ontario M5T 1R8, Canada. clement.hamani@uhn.on.ca

Abstract

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.

PMID:
19819426
DOI:
10.1016/j.biopsych.2009.08.025
[Indexed for MEDLINE]

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