Effects of iTBS-rTMS on the Behavioral Phenotype of a Rat Model of Maternal Immune Activation

Nadine Rittweger; Tanja Ishorst; Gleb Barmashenko; Verena Aliane; Christine Winter; Klaus Funke

doi:10.3389/fnbeh.2021.670699

Effects of iTBS-rTMS on the Behavioral Phenotype of a Rat Model of Maternal Immune Activation

Front Behav Neurosci. 2021 Apr 21:15:670699. doi: 10.3389/fnbeh.2021.670699. eCollection 2021.

Authors

Nadine Rittweger¹, Tanja Ishorst¹, Gleb Barmashenko^{1

2}, Verena Aliane¹, Christine Winter^{3

4}, Klaus Funke¹

Affiliations

¹ Department of Neurophysiology, Medical Faculty, Ruhr-University, Bochum, Germany.
² AIO-Studien-gGmbH, Berlin, Germany.
³ Department of Psychiatry and Psychotherapy, Charité University Medicine Berlin, Berlin, Germany.
⁴ Department of Psychiatry and Psychotherapy, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

Abstract

Repetitive transcranial magnetic stimulation (rTMS) is considered a promising therapeutic tool for treating neuropsychiatric diseases. Previously, we found intermittent theta-burst stimulation (iTBS) rTMS to be most effective in modulating cortical excitation-inhibition balance in rats, accompanied by improved cortical sensory processing and sensory learning performance. Using an animal schizophrenia model based on maternal immune activation (MIA) we tested if iTBS applied to either adult or juvenile rats can affect the behavioral phenotype in a therapeutic or preventive manner, respectively. In a sham-controlled fashion, iTBS effects in MIA rats were compared with rats receiving vehicle NaCl injection instead of the synthetic viral strand. Prior to iTBS, adult MIA rats showed deficits in sensory gating, as tested with prepulse inhibition (PPI) of the acoustic startle reflex, and deficits in novel object recognition (NOR). No differences between MIA and control rats were evident with regard to signs of anxiety, anhedonia and depression but MIA rats were somewhat superior to controls during the training phase of Morris Water Maze (MWM) test. MIA but not control rats significantly improved in PPI following iTBS at adulthood but without significant differences between verum and sham application. If applied during adolescence, verum but not sham-iTBS improved NOR at adulthood but no difference in PPI was evident in rats treated either with sham or verum-iTBS. MIA and control rat responses to sham-iTBS applied at adulthood differed remarkably, indicating a different physiological reaction to the experimental experiences. Although verum-iTBS was not superior to sham-iTBS, MIA rats seemed to benefit from the treatment procedure in general, since differences-in relation to control rats declined or disappeared. Even if classical placebo effects can be excluded, motor or cognitive challenges or the entire handling procedure during the experiments appear to alleviate the behavioral impairments of MIA rats.

Keywords: animal model; behavioral phenotypes; history of experience; iTBS; maternal immune stimulation; rTMS; schizophrenia; sham stimulation.