title: Mapping brain regions in which deep brain stimulation affects schizophrenia-like behavior in two rat models of schizophrenia.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité Campus Mitte, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Klein
authors.forename: Ravit
authors.initials: R
authors.lastname: Hadar
authors.forename: Thomas
authors.initials: T
authors.lastname: Götz
authors.forename: Anika
authors.initials: A
authors.lastname: Männer
authors.forename: Claudia
authors.initials: C
authors.lastname: Eberhardt
authors.forename: Jacopo
authors.initials: J
authors.lastname: Baldassarri
authors.forename: Timo Torsten
authors.initials: TT
authors.lastname: Schmidt
authors.forename: Andreas
authors.initials: A
authors.lastname: Kupsch
authors.forename: Andreas
authors.initials: A
authors.lastname: Heinz
authors.forename: Rudolf
authors.initials: R
authors.lastname: Morgenstern
authors.forename: Miriam
authors.initials: M
authors.lastname: Schneider
authors.forename: Ina
authors.initials: I
authors.lastname: Weiner
authors.forename: Christine
authors.initials: C
authors.lastname: Winter
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D046690:Deep Brain Stimulation / Q000379:methods*; D004195:Disease Models, Animal; D051381:Rats; D017208:Rats, Wistar; D012559:Schizophrenia / Q000503:physiopathology*
keywords: Deep brain stimulation; Poly I:C; Prepulse inhibition; Schizophrenia; WIN