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 1ms pulse-width, 100 pulses/s, 1s duration, ranging from 5.5mA to 10mA. 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.