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Article: Electrical stimulation alleviates depressive-like behaviors of rats: investigation of brain targets and potential mechanisms

TitleElectrical stimulation alleviates depressive-like behaviors of rats: investigation of brain targets and potential mechanisms
Authors
Issue Date2015
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/tp/index.html
Citation
Translational Psychiatry, 2015, v. 5 n. 3, p. Article no. e535 How to Cite?
AbstractDeep brain stimulation (DBS) is a promising therapy for patients with refractory depression. However, key questions remain with regard to which brain target(s) should be used for stimulation, and which mechanisms underlie the therapeutic effects. Here, we investigated the effect of DBS, with low- and high-frequency stimulation (LFS, HFS), in different brain regions (ventromedial prefrontal cortex, vmPFC; cingulate cortex, Cg; nucleus accumbens (NAc) core or shell; lateral habenula, LHb; and ventral tegmental area) on a variety of depressive-like behaviors using rat models. In the naive animal study, we found that HFS of the Cg, vmPFC, NAc core and LHb reduced anxiety levels and increased motivation for food. In the chronic unpredictable stress model, there was a robust depressive-like behavioral phenotype. Moreover, vmPFC HFS, in a comparison of all stimulated targets, produced the most profound antidepressant effects with enhanced hedonia, reduced anxiety and decreased forced-swim immobility. In the following set of electrophysiological and histochemical experiments designed to unravel some of the underlying mechanisms, we found that vmPFC HFS evoked a specific modulation of the serotonergic neurons in the dorsal raphe nucleus (DRN), which have long been linked to mood. Finally, using a neuronal mapping approach by means of c-Fos expression, we found that vmPFC HFS modulated a brain circuit linked to the DRN and known to be involved in affect. In conclusion, HFS of the vmPFC produced the most potent antidepressant effects in naive rats and rats subjected to stress by mechanisms also including the DRN.
Persistent Identifierhttp://hdl.handle.net/10722/227906
ISSN
2015 Impact Factor: 5.538
2015 SCImago Journal Rankings: 3.057
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLim, LW-
dc.contributor.authorPrickaerts, J-
dc.contributor.authorHuguet, G-
dc.contributor.authorKadar, E-
dc.contributor.authorHartung, H-
dc.contributor.authorSharp, T-
dc.contributor.authorTemel, Y-
dc.date.accessioned2016-07-25T01:28:24Z-
dc.date.available2016-07-25T01:28:24Z-
dc.date.issued2015-
dc.identifier.citationTranslational Psychiatry, 2015, v. 5 n. 3, p. Article no. e535-
dc.identifier.issn2158-3188-
dc.identifier.urihttp://hdl.handle.net/10722/227906-
dc.description.abstractDeep brain stimulation (DBS) is a promising therapy for patients with refractory depression. However, key questions remain with regard to which brain target(s) should be used for stimulation, and which mechanisms underlie the therapeutic effects. Here, we investigated the effect of DBS, with low- and high-frequency stimulation (LFS, HFS), in different brain regions (ventromedial prefrontal cortex, vmPFC; cingulate cortex, Cg; nucleus accumbens (NAc) core or shell; lateral habenula, LHb; and ventral tegmental area) on a variety of depressive-like behaviors using rat models. In the naive animal study, we found that HFS of the Cg, vmPFC, NAc core and LHb reduced anxiety levels and increased motivation for food. In the chronic unpredictable stress model, there was a robust depressive-like behavioral phenotype. Moreover, vmPFC HFS, in a comparison of all stimulated targets, produced the most profound antidepressant effects with enhanced hedonia, reduced anxiety and decreased forced-swim immobility. In the following set of electrophysiological and histochemical experiments designed to unravel some of the underlying mechanisms, we found that vmPFC HFS evoked a specific modulation of the serotonergic neurons in the dorsal raphe nucleus (DRN), which have long been linked to mood. Finally, using a neuronal mapping approach by means of c-Fos expression, we found that vmPFC HFS modulated a brain circuit linked to the DRN and known to be involved in affect. In conclusion, HFS of the vmPFC produced the most potent antidepressant effects in naive rats and rats subjected to stress by mechanisms also including the DRN.-
dc.languageeng-
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/tp/index.html-
dc.relation.ispartofTranslational Psychiatry-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleElectrical stimulation alleviates depressive-like behaviors of rats: investigation of brain targets and potential mechanisms-
dc.typeArticle-
dc.identifier.emailLim, LW: limlw@hku.hk-
dc.identifier.authorityLim, LW=rp02088-
dc.description.naturepostprint-
dc.identifier.doi10.1038/tp.2015.24-
dc.identifier.pmid25826110-
dc.identifier.pmcidPMC4354354-
dc.identifier.hkuros260032-
dc.identifier.volume5-
dc.identifier.issue3-
dc.identifier.spageArticle no. e535-
dc.identifier.epageArticle no. e535-
dc.identifier.isiWOS:000367655000001-
dc.publisher.placeUnited Kingdom-

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