Testing different paradigms to optimize antidepressant deep brain stimulation in different rat models of depression

• Verfasst von: Rummel, Julia [VerfasserIn]
• Verfasst von: Sartorius, Alexander [VerfasserIn]
• Verfasst von: Vollmayr, Barbara [VerfasserIn]
• Titel: Testing different paradigms to optimize antidepressant deep brain stimulation in different rat models of depression
• Verf.angabe: Julia Rummel, Mareike Voget, Ravit Hadar, Samuel Ewing, Reinhard Sohr, Julia Klein, Alexander Sartorius, Andreas Heinz, Aleksander A. Mathé, Barbara Vollmayr, Christine Winter
• E-Jahr: 2016
• Jahr: October 2016
• Umfang: 10 S.
• Fussnoten: Gesehen am 17.07.2019 ; Available online 18 June 2016
• Titel Quelle: Enthalten in: Journal of psychiatric research
• Ort Quelle: Amsterdam [u.a.] : Elsevier Science, 1961
• Jahr Quelle: 2016
• Band/Heft Quelle: 81(2016), Seite 36-45
• ISSN Quelle: 1879-1379
• DOI: doi:10.1016/j.jpsychires.2016.06.016
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Deep brain stimulation
• Sach-SW: Depression
• Sach-SW: Parameter settings
• Sach-SW: Rat model
• K10plus-PPN: 1669318702

Abstract

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.