Electrical stimulation alleviates depressive-like behaviors of rats: investigation of brain targets and potential mechanisms
Open accessAbstract
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.
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The sweet spot is in the high-frequency range of 100-150 Hz, which is also supported by animal studies.
“the sweet spot is in the high-frequency range (100-150 Hz) [103], which is also supported by animal studies [104,105].”
From Deep brain stimulation for depression. (2022) · cites this paper as [105]
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Self-citationLim, L. W., Blokland, A., Tan, S. K. H., Vlamings, R., Sesia, T., Aziz-Mohammadi, M., Visser-Vandewalle, V. E. R. M., Steinbusch, H. W. M., Schruers, K. R. J., & Temel, Y. (2010) · Experimental Neurology · doi:10.1016/j.expneurol.2010.08.035 · Cited by 21 · see citing works
Self-citationJahanshahi, A., Lim, L. W., Steinbusch, H. W. M., et al. (2010) · Neuroscience Letters · doi:10.1016/j.neulet.2010.02.038 · Cited by 16 · see citing works
Self-citationNeurosurgical Treatments of Depression
Temel, Y., & Lim, L. W. (2012) · Current topics in behavioral neurosciences · doi:10.1007/7854_2012_222 · Cited by 15 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- Schlaepfer TE Cohen MX Frick C Kosel M Brodesser D Axmacher N Deep brain stimulation to reward circuitry alleviates anhedonia in refractory major depression Neuropsychopharmacology 2008 33 368 377 17429407
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- Authors
- Lim, L. W., Prickaerts, J., Huguet, G., Kadar, E., Hartung, H., Sharp, T., & Temel, Y.
- Affiliations
- Nanyang Technological University (SG)
- Maastricht University (NL)
- Universitat de Girona (ES)
- University of Oxford (GB)
- Corresponding author
- Lim, L W
- Venue
- Translational Psychiatry
- Published
- 2015-03-31
- Volume
- 5
- Issue
- 3
- Pages
- e535-e535
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC4354354
- OpenAlex
- W1966449086
- Cited by
- 116
- References
- 99
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 5 · 2023: 10 · 2022: 11 · 2021: 11 · 2020: 18 · 2019: 12 · 2018: 12 · 2017: 11 · 2016: 10 · 2015: 6
- FWCI
- 9.17
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Translational Psychiatry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, cc-by)
- Universitat de Girona Digital Repository (Universitat de Girona) (acceptedVersion, cc-by)
- RECERCAT (Consorci de Serveis Universitaris de Catalunya) (acceptedVersion, other-oa)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- RECERCAT (Consorci de Serveis Universitaris de Catalunya) (submittedVersion, other-oa)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Greater South Information System
- Funders
- Parkinson's UK
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (016.096.032)
- Topics
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Keywords
- deep brain stimulation, treatment-resistant depression, ventromedial prefrontal cortex, high-frequency stimulation, low-frequency stimulation, dorsal raphe nucleus, serotonergic neurons, chronic unpredictable mild stress, depression-like behavior, anxiety, food motivation, Fos expression, brain circuits, antidepressant mechanism, lateral habenula, nucleus accumbens, cingulate cortex, ventral tegmental area
- MeSH terms
- Analysis of Variance, Animals, Behavior, Animal, Brain, Depression, Disease Models, Animal, Male, Serotonin, Rats, Sprague-Dawley, Deep Brain Stimulation, Rats
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