Testing different paradigms to optimize antidepressant deep brain stimulation in different rat models of depression
Deep brain stimulation (DBS) of several targets induces beneficial responses in approximately 60% of patients suffering from treatment-resistant depression (TRD). The remaining 40% indicate that these stimulation sites do not bear therapeutic relevance for all TRD patients and consequently DBS-targe...
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| Main Authors: | , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
October 2016
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| In: |
Journal of psychiatric research
Year: 2016, Volume: 81, Pages: 36-45 |
| ISSN: | 1879-1379 |
| DOI: | 10.1016/j.jpsychires.2016.06.016 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1016/j.jpsychires.2016.06.016 Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S0022395616301236 
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| Author Notes: | Julia Rummel, Mareike Voget, Ravit Hadar, Samuel Ewing, Reinhard Sohr, Julia Klein, Alexander Sartorius, Andreas Heinz, Aleksander A. Mathé, Barbara Vollmayr, Christine Winter |
| Summary: | Deep brain stimulation (DBS) of several targets induces beneficial responses in approximately 60% of patients suffering from treatment-resistant depression (TRD). The remaining 40% indicate that these stimulation sites do not bear therapeutic relevance for all TRD patients and consequently DBS-targets should be selected according to individual symptom profiles. We here used two animal models of depression known to have different genetic backgrounds and behavioral responses: the therapy-responsive Flinders sensitive line (FSL) and the therapy-refractory congenitally learned helpless rats (cLH) to study symptom-specific DBS effects i) of different brain sites ii) at different stimulation parameters, and iii) at different expressions of the disease. Sham-stimulation/DBS was applied chronic-intermittently or chronic-continuously to either the ventromedial prefrontal cortex (vmPFC, rodent equivalent to subgenual cingulate), nucleus accumbens (Nacc) or subthalamic nucleus (STN), and effects were studied on different depression-associated behaviors, i.e. anhedonia, immobility/behavioral despair and learned helplessness. Biochemical substrates of behaviorally effective versus ineffective DBS were analyzed using in-vivo microdialysis and post-mortem high-performance liquid chromatography (HPLC). We found that i) vmPFC-DBS outperforms Nacc-DBS, ii) STN-DBS increases depressive states, iii) chronic-continuous DBS does not add benefits compared to chronic-intermittent DBS, iv) DBS-efficacy depends on the disease expression modeled and iv) antidepressant DBS is associated with an increase in serotonin turnover alongside site-specific reductions in serotonin contents. The reported limited effectiveness of vmPFC DBS suggests that future research may consider the specific disease expression, investigation of different DBS-targets and alternative parameter settings. |
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| Item Description: | Gesehen am 17.07.2019 Available online 18 June 2016 |
| Physical Description: | Online Resource |
| ISSN: | 1879-1379 |
| DOI: | 10.1016/j.jpsychires.2016.06.016 |