Abnormal Motor Activity and Thermoregulation in a Schizophrenia Rat Model for Translational Science

Abstract

BackgroundSchizophrenia is accompanied by altered motor activity and abnormal thermoregulation; therefore, the presence of these symptoms can enhance the face validity of a schizophrenia animal model. The goal was to characterize these parameters in freely moving condition of a new substrain of rats showing several schizophrenia-related alterations.MethodsMale Wistar rats were used: the new substrain housed individually (for four weeks) and treated subchronically with ketamine, and naive animals without any manipulations. Adult animals were implanted with E-Mitter transponders intraabdominally to record body temperature and locomotor activity continuously. The circadian rhythm of these parameters and the acute effects of changes in light conditions were analyzed under undisturbed circumstances, and the effects of different interventions (handling, bed changing or intraperitoneal vehicle injection) were also determined.ResultsDecreased motor activity with fragmented pattern was observed in the new substrain. However, these animals had higher body temperature during the active phase, and they showed wider range of its alterations, too. The changes in light conditions and different interventions produced blunted hyperactivity and altered body temperature responses in the new substrain. Poincaré plot analysis of body temperature revealed enhanced short- and long-term variabilities during the active phase compared to the inactive phase in both groups. Furthermore, the new substrain showed increased short- and long-term variabilities with lower degree of asymmetry suggesting autonomic dysregulation.ConclusionsIn summary, the new substrain with schizophrenia-related phenomena showed disturbed motor activity and thermoregulation suggesting that these objectively determined parameters can be biomarkers in translational research.

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].…”