Electrophysiological alterations in a complex rat model of schizophrenia

Abstract

The validation of the translational utility of this new rat substrain by electrophysiological investigations revealed that these rats show abnormalities that may model a part of the neurophysiological deficits observed in schizophrenia.

Characterization of exploratory activity and learning ability of healthy and “schizophrenia-like” rats in a square corridor system (AMBITUS)

“…Starting from a population of outbred Wistar rats, animals with the highest level of disturbances in these parameters were used for selective breeding throughout several generations (Petrovszki et al, 2013;Kekesi et al, 2015;Horvath et al, 2015Horvath et al, , 2016Szűcs et al, 2016a, b).…”

“…These animals showed several signs of schizophrenia, i.e., disturbed sensory gating, motor activity, pain sensitivity, cognitive function and thermoregulation; electrophysiological alterations in electroencephalographic waves; changes in the signalling properties of the cannabinoid and opioid receptors in different brain regions (Petrovszki et al, 2013;Kekesi et al, 2015;Horvath et al, 2015Horvath et al, , 2016Szűcs et al, 2016a, b). The evaluation of these animals in this test may give further evidence about the reliability of this test tool for the investigation of animals with disturbed cognitive function.…”

Cognitive training improves the disturbed behavioral architecture of schizophrenia-like rats, “Wisket”

“…Based on our earlier studies, both control and Wisket rats, after weaning at 3 weeks of age, were tested in the tail-flick (TF) test (48°C hot water) to assess their basal acute heat pain sensitivity (Table 1.) [3][4][5][6][7][8][9]. Then the Wisket animals were housed individually for 28 days, and were treated with intraperitoneal ketamine (Calypsol, Gedeon Richter Plc., Budapest, Hungary; 30 mg/kg, 4 ml/kg, daily, 5 times/ week, 15 injections in total) from 5 to 7 weeks of age.…”

“…However, as far as the validity of the animal model itself is concerned, this is not really an issue. In our previous papers we provided ample evidence that the new substrain after the complex treatment has the highest validity as a schizophrenia model compared to the appropriated control groups [3], and from that time we concentrated to the characterization of this model from several aspects [4][5][6][7][8][9]. The contribution of the genetic or environmental factors separately to the different signs is indeed an interesting theoretical question, however, it also raises ethical concerns.…”

“…To achieve a high constructive validity, we developed a complex, chronic, "multiple hit" rat model, named Wisket (the selective breeding originated from Wistar strain after postweaning ISolation and subchronic KETamine treatment) [3]. This model shows several symptoms of schizophrenia, such as disturbed sensory gating, pain sensitivity and thermoregulation, electroencephalographic alterations and changed opioid and cannabinoid receptor functions (as face validity) [3][4][5][6][7][8][9]. Furthermore, decreased exploratory activity and cognitive dysfunctions have also been described in short-term paradigms of learning tests [3,4,7].…”