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- Publisher Website: 10.1038/tp.2015.24
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- PMID: 25826110
- WOS: WOS:000367655000001
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Article: Electrical stimulation alleviates depressive-like behaviors of rats: investigation of brain targets and potential mechanisms
Title | Electrical stimulation alleviates depressive-like behaviors of rats: investigation of brain targets and potential mechanisms |
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Authors | |
Issue Date | 2015 |
Publisher | Nature 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? |
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. |
Persistent Identifier | http://hdl.handle.net/10722/227906 |
ISSN | 2023 Impact Factor: 5.8 2023 SCImago Journal Rankings: 2.203 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Lim, LW | - |
dc.contributor.author | Prickaerts, J | - |
dc.contributor.author | Huguet, G | - |
dc.contributor.author | Kadar, E | - |
dc.contributor.author | Hartung, H | - |
dc.contributor.author | Sharp, T | - |
dc.contributor.author | Temel, Y | - |
dc.date.accessioned | 2016-07-25T01:28:24Z | - |
dc.date.available | 2016-07-25T01:28:24Z | - |
dc.date.issued | 2015 | - |
dc.identifier.citation | Translational Psychiatry, 2015, v. 5 n. 3, p. Article no. e535 | - |
dc.identifier.issn | 2158-3188 | - |
dc.identifier.uri | http://hdl.handle.net/10722/227906 | - |
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.language | eng | - |
dc.publisher | Nature Publishing Group. The Journal's web site is located at http://www.nature.com/tp/index.html | - |
dc.relation.ispartof | Translational Psychiatry | - |
dc.title | Electrical stimulation alleviates depressive-like behaviors of rats: investigation of brain targets and potential mechanisms | - |
dc.type | Article | - |
dc.identifier.email | Lim, LW: limlw@hku.hk | - |
dc.identifier.authority | Lim, LW=rp02088 | - |
dc.description.nature | postprint | - |
dc.identifier.doi | 10.1038/tp.2015.24 | - |
dc.identifier.pmid | 25826110 | - |
dc.identifier.pmcid | PMC4354354 | - |
dc.identifier.scopus | eid_2-s2.0-84989917980 | - |
dc.identifier.hkuros | 260032 | - |
dc.identifier.volume | 5 | - |
dc.identifier.issue | 3 | - |
dc.identifier.spage | Article no. e535 | - |
dc.identifier.epage | Article no. e535 | - |
dc.identifier.isi | WOS:000367655000001 | - |
dc.publisher.place | United Kingdom | - |
dc.identifier.issnl | 2158-3188 | - |