期刊
CEREBRAL CORTEX
卷 26, 期 6, 页码 2778-2789出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/cercor/bhv133
关键词
c-Fos; dorsal raphe nucleus; glutamate; microdialysis; serotonin
资金
- Junta de Andalucia [CTS-510, CTS-7748]
- Instituto de Salud Carlos III
- Subdireccion General de Evaluacion y Fomento de la Investigacion (FIS) [PI10-01103, PI13-00038, PI12-00915]
- European Regional Development Fund
- Centro de Investigacion Biomedica en Red de Salud Mental (CIBERSAM, Intramural Project Grant) [P91G]
- Generalitat de Catalunya [2009SGR220]
- Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS)
Although deep brain stimulation (DBS) has been used with success in treatment-resistant depression, little is known about its mechanism of action. We examined the antidepressant-like activity of short (1 h) DBS applied to the infralimbic prefrontal cortex in the forced swim test (FST) and the novelty-suppressed feeding test (NSFT). We also used in vivo microdialysis to evaluate the release of glutamate, gamma-aminobutyric acid, serotonin, dopamine, and noradrenaline in the prefrontal cortex and c-Fos immunohistochemistry to determine the brain regions activated by DBS. One hour of DBS of the infralimbic prefrontal cortex has antidepressant-like effects in FST and NSFT, and increases prefrontal efflux of glutamate, which would activate AMPA receptors (AMPARs). This effect is specific of the infralimbic area since it is not observed after DBS of the prelimbic subregion. The activation of prefrontal AMPARs would result in a stimulation of prefrontal output to the brainstem, thus increasing serotonin, dopamine, and noradrenaline in the prefrontal cortex. Further, the activation of prefrontal AMPARs is necessary and sufficient condition for the antidepressant response of 1 h DBS.
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