Mapping Brain Regions in Which Deep Brain Stimulation Affects Schizophrenia-Like Behavior in Two Rat Models of Schizophrenia
Background and Objectives: The development of more efficient treatment remains a major unmet need in the realm of schizophrenia disease. Using the maternal immune stimulation and the pubertal cannabinoid administration rat model of schizophrenia, the present study aimed at testing the hypothesis tha...
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doaj-500dafff8dcd41efb3494b865ab65d312021-03-18T04:36:16ZengElsevierBrain Stimulation1935-861X2013-07-0164490499Mapping Brain Regions in Which Deep Brain Stimulation Affects Schizophrenia-Like Behavior in Two Rat Models of SchizophreniaJulia Klein0Ravit Hadar1Thomas Götz2Anika Männer3Claudia Eberhardt4Jacopo Baldassarri5Timo Torsten Schmidt6Andreas Kupsch7Andreas Heinz8Rudolf Morgenstern9Miriam Schneider10Ina Weiner11Christine Winter12Department of Psychiatry and Psychotherapy, Charité Campus Mitte, GermanyDepartment of Psychiatry and Psychotherapy, Technical University Dresden, GermanyDepartment of Psychiatry and Psychotherapy, Technical University Dresden, GermanyDepartment of Psychiatry and Psychotherapy, Charité Campus Mitte, GermanyDepartment of Psychiatry and Psychotherapy, Charité Campus Mitte, GermanyDepartment of Psychiatry and Psychotherapy, Charité Campus Mitte, GermanyDepartment of Psychiatry and Psychotherapy, Charité Campus Mitte, GermanyDepartment of Neurology, Charité Campus Virchow Klinikum, GermanyDepartment of Psychiatry and Psychotherapy, Charité Campus Mitte, GermanyInstitute of Pharmacology and Toxicology, Charité Campus Mitte, University Medicine Berlin, GermanyDepartment of Developmental Psychopharmacology, Central Institute of Mental Health, Mannheim, GermanyDepartment of Psychology, Tel Aviv University, Tel Aviv, IsraelDepartment of Psychiatry and Psychotherapy, Technical University Dresden, Germany; Corresponding author. Tel.: +49 351 458 4450; fax: +49 351 458 5350.Background and Objectives: The development of more efficient treatment remains a major unmet need in the realm of schizophrenia disease. Using the maternal immune stimulation and the pubertal cannabinoid administration rat model of schizophrenia, the present study aimed at testing the hypothesis that deep brain stimulation (DBS) serves as a novel therapeutic technique for this disorder. Methods: Adult offspring of dams, treated with the immune activating agent poly I:C (4 mg/kg, n = 50) or saline (n = 50), underwent bilateral stereotactic electrode implantation into one of the following brain regions: subthalamic nucleus (STN, n = 12/10), entopeduncularis nucleus (EP, n = 10/11), globus pallidus (GP, n = 10/10), medial prefrontal cortex (mPFC, n = 8/8), or dorsomedial thalamus (DM, n = 10/11). Adult rats treated with the CB1 receptor agonist WIN 55,212-2 (WIN, n = 16) or saline (n = 12) during puberty were bilaterally implanted with electrodes into either the mPFC (n = 8/6) or the DM (n = 8/6). After a post-operative recovery period of one week, all rats were tested on a well-established cross-species phenomenon that is disrupted in schizophrenia, the pre-pulse inhibition (PPI) of the acoustic startle reflex (ASR) under different DBS conditions. Results: Poly I:C induced deficits in PPI of the ASR were normalized upon DBS. DBS effects depended on both stimulation target and stimulation parameters. Most prominent effects were found under DBS at high frequencies in the mPFC and DM. These effects were replicated in the pubertal WIN administration rat model of schizophrenia. Conclusions: Brain regions, in which DBS normalized PPI deficits, might be of therapeutic relevance to the treatment of schizophrenia. Results imply that DBS could be considered a plausible therapeutic technique in the realm of schizophrenia disease.http://www.sciencedirect.com/science/article/pii/S1935861X12001581Deep brain stimulationSchizophreniaPrepulse inhibitionPoly I:CWIN |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Julia Klein Ravit Hadar Thomas Götz Anika Männer Claudia Eberhardt Jacopo Baldassarri Timo Torsten Schmidt Andreas Kupsch Andreas Heinz Rudolf Morgenstern Miriam Schneider Ina Weiner Christine Winter |
spellingShingle |
Julia Klein Ravit Hadar Thomas Götz Anika Männer Claudia Eberhardt Jacopo Baldassarri Timo Torsten Schmidt Andreas Kupsch Andreas Heinz Rudolf Morgenstern Miriam Schneider Ina Weiner Christine Winter Mapping Brain Regions in Which Deep Brain Stimulation Affects Schizophrenia-Like Behavior in Two Rat Models of Schizophrenia Brain Stimulation Deep brain stimulation Schizophrenia Prepulse inhibition Poly I:C WIN |
author_facet |
Julia Klein Ravit Hadar Thomas Götz Anika Männer Claudia Eberhardt Jacopo Baldassarri Timo Torsten Schmidt Andreas Kupsch Andreas Heinz Rudolf Morgenstern Miriam Schneider Ina Weiner Christine Winter |
author_sort |
Julia Klein |
title |
Mapping Brain Regions in Which Deep Brain Stimulation Affects Schizophrenia-Like Behavior in Two Rat Models of Schizophrenia |
title_short |
Mapping Brain Regions in Which Deep Brain Stimulation Affects Schizophrenia-Like Behavior in Two Rat Models of Schizophrenia |
title_full |
Mapping Brain Regions in Which Deep Brain Stimulation Affects Schizophrenia-Like Behavior in Two Rat Models of Schizophrenia |
title_fullStr |
Mapping Brain Regions in Which Deep Brain Stimulation Affects Schizophrenia-Like Behavior in Two Rat Models of Schizophrenia |
title_full_unstemmed |
Mapping Brain Regions in Which Deep Brain Stimulation Affects Schizophrenia-Like Behavior in Two Rat Models of Schizophrenia |
title_sort |
mapping brain regions in which deep brain stimulation affects schizophrenia-like behavior in two rat models of schizophrenia |
publisher |
Elsevier |
series |
Brain Stimulation |
issn |
1935-861X |
publishDate |
2013-07-01 |
description |
Background and Objectives: The development of more efficient treatment remains a major unmet need in the realm of schizophrenia disease. Using the maternal immune stimulation and the pubertal cannabinoid administration rat model of schizophrenia, the present study aimed at testing the hypothesis that deep brain stimulation (DBS) serves as a novel therapeutic technique for this disorder. Methods: Adult offspring of dams, treated with the immune activating agent poly I:C (4 mg/kg, n = 50) or saline (n = 50), underwent bilateral stereotactic electrode implantation into one of the following brain regions: subthalamic nucleus (STN, n = 12/10), entopeduncularis nucleus (EP, n = 10/11), globus pallidus (GP, n = 10/10), medial prefrontal cortex (mPFC, n = 8/8), or dorsomedial thalamus (DM, n = 10/11). Adult rats treated with the CB1 receptor agonist WIN 55,212-2 (WIN, n = 16) or saline (n = 12) during puberty were bilaterally implanted with electrodes into either the mPFC (n = 8/6) or the DM (n = 8/6). After a post-operative recovery period of one week, all rats were tested on a well-established cross-species phenomenon that is disrupted in schizophrenia, the pre-pulse inhibition (PPI) of the acoustic startle reflex (ASR) under different DBS conditions. Results: Poly I:C induced deficits in PPI of the ASR were normalized upon DBS. DBS effects depended on both stimulation target and stimulation parameters. Most prominent effects were found under DBS at high frequencies in the mPFC and DM. These effects were replicated in the pubertal WIN administration rat model of schizophrenia. Conclusions: Brain regions, in which DBS normalized PPI deficits, might be of therapeutic relevance to the treatment of schizophrenia. Results imply that DBS could be considered a plausible therapeutic technique in the realm of schizophrenia disease. |
topic |
Deep brain stimulation Schizophrenia Prepulse inhibition Poly I:C WIN |
url |
http://www.sciencedirect.com/science/article/pii/S1935861X12001581 |
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