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Testing different paradigms to optimize antidepressant deep brain stimulation in different rat models of depression.
Rummel, Julia; Voget, Mareike; Hadar, Ravit; Ewing, Samuel; Sohr, Reinhard; Klein, Julia; Sartorius, Alexander; Heinz, Andreas; Mathé, Aleksander A; Vollmayr, Barbara; Winter, Christine.
Afiliación
  • Rummel J; Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstraße 74, 01307 Dresden, Germany; International Graduate Program Medical Neurosciences, Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
  • Voget M; Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstraße 74, 01307 Dresden, Germany; International Graduate Program Medical Neurosciences, Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
  • Hadar R; Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstraße 74, 01307 Dresden, Germany.
  • Ewing S; Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstraße 74, 01307 Dresden, Germany.
  • Sohr R; Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstraße 74, 01307 Dresden, Germany.
  • Klein J; Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
  • Sartorius A; Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J 5, 68159 Mannheim, Germany.
  • Heinz A; Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
  • Mathé AA; Department of Clinical Neuroscience, Karolinska Institutet, St Görans Hospital, Tomtebodavägen 18A, 17177 Stockholm, Sweden.
  • Vollmayr B; Research Group Animal Models in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J 5, 68159 Mannheim, Germany.
  • Winter C; Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstraße 74, 01307 Dresden, Germany. Electronic address: christine.winter@uniklinikum-dresden.de.
J Psychiatr Res ; 81: 36-45, 2016 10.
Article en En | MEDLINE | ID: mdl-27367210
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Estimulación Encefálica Profunda / Depresión / Modelos Animales de Enfermedad Límite: Animals Idioma: En Revista: J Psychiatr Res Año: 2016 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Estimulación Encefálica Profunda / Depresión / Modelos Animales de Enfermedad Límite: Animals Idioma: En Revista: J Psychiatr Res Año: 2016 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido