title: Cortical electroconvulsive stimulation alleviates breeding-induced prepulse inhibition deficit in rats.
abstract: In patients with medical-refractory schizophrenia electroconvulsive therapy (ECT), i.e., the induction of therapeutic seizures via cortical surface electrodes, is effectively used. Electroconvulsive stimulation (ECS) in rodents simulates ECT in humans and is applied to investigate the mechanisms underlying this treatment. Experimentally-induced reduced prepulse inhibition (PPI) of the acoustic startle response (ASR), i.e., the reduction of the startle response to an intense acoustic stimulus when this stimulus is shortly preceded by a weaker not-startling stimulus, serves as an endophenotype for neuropsychiatric disorders that are accompanied by disturbed sensorimotor gating, such as schizophrenia. Here we used rats selectively bred for high and low PPI to evaluate whether bifrontal cortical ECS would affect PPI. For this purpose, cortical screw electrodes were stereotactically implanted above the frontal cortex. After recovery ECS was applied for five consecutive days with stimuli of 1 ms pulse-width, 100 pulses/s, 1 s duration, ranging from 5.5 mA to 10 mA. PPI of ASR was measured one day before ECS, and on days 1, 7, and 14 after the last ECS. In rats with breeding-induced low PPI ECS increased PPI one week after stimulation. In contrast, ECS decreased PPI in rats with high PPI on the first day after stimulation. The reaction to the startle impulse was reduced by ECS without difference between groups. This work provides evidence that rats with breeding-induced high or low PPI could be used to further investigate the underlying mechanisms of ECT in neuropsychiatric disorders with disturbed sensorimotor gating like schizophrenia.
authors.affiliation: Department of Neurosurgery, Hannover Medical School, Carl-Neuberg-Str.1, 30625 Hannover, Germany. Electronic address: john.nadine@mh-hannover.de.
authors.forename: Nadine
authors.initials: N
authors.lastname: John
authors.affiliation: Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine, Bünteweg 17, 30559 Hannover, Germany; Molecular Neuroscience Laboratory, Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Carl-Neuberg-Str.1, 30625 Hannover, Germany.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Theilmann
authors.affiliation: Molecular Neuroscience Laboratory, Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Carl-Neuberg-Str.1, 30625 Hannover, Germany.
authors.forename: Helge
authors.initials: H
authors.lastname: Frieling
authors.affiliation: Department of Neurosurgery, Hannover Medical School, Carl-Neuberg-Str.1, 30625 Hannover, Germany.
authors.forename: Joachim K
authors.initials: JK
authors.lastname: Krauss
authors.affiliation: Department of Neurosurgery, Hannover Medical School, Carl-Neuberg-Str.1, 30625 Hannover, Germany.
authors.forename: Mesbah
authors.initials: M
authors.lastname: Alam
authors.affiliation: Department of Neurosurgery, Hannover Medical School, Carl-Neuberg-Str.1, 30625 Hannover, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Schwabe
authors.affiliation: Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine, Bünteweg 17, 30559 Hannover, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Brandt
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D002540:Cerebral Cortex / Q000502:physiology*; D004558:Electric Stimulation; D008297:Male; D065808:Prepulse Inhibition / Q000235:genetics / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013216:Reflex, Startle / Q000235:genetics / Q000502:physiology*; D055139:Sensory Gating / Q000235:genetics / Q000502:physiology*
keywords: Animal model; Electroconvulsive stimulation; Prepulse inhibition; Rat; Schizophrenia; Sensorimotor gating