Electrical stimulation alleviates depressive-like behaviors of rats: investigation of brain targets and potential mechanisms
dc.contributor.author
dc.date.accessioned
2018-04-09T08:13:06Z
dc.date.available
2018-04-09T08:13:06Z
dc.date.issued
2015-03-31
dc.identifier.uri
dc.description.abstract
Deep 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.format.mimetype
application/pdf
dc.language.iso
eng
dc.publisher
Nature Publishing Group
dc.relation.isformatof
Reproducció digital del document publicat a: https://doi.org/10.1038/tp.2015.24
dc.relation.ispartof
Translational Psychiatry, 2015, vol. 5, p. e535
dc.relation.ispartofseries
Articles publicats (D-B)
dc.rights
Attribution 4.0 Spain
dc.rights.uri
dc.title
Electrical stimulation alleviates depressive-like behaviors of rats: investigation of brain targets and potential mechanisms
dc.type
info:eu-repo/semantics/article
dc.rights.accessRights
info:eu-repo/semantics/openAccess
dc.type.version
info:eu-repo/semantics/publishedVersion
dc.identifier.doi
dc.identifier.idgrec
023856
dc.type.peerreviewed
peer-reviewed
dc.identifier.eissn
2158-3188