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

Schizophrenia 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.Male 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.Decreased 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.In 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

Schedule of the experimental protocol for selective breeding and behavioral testing.

<p>Abbreviations: TF: tail-flick test, PPI: prepulse inhibition test, HB: hole-board test.</p><p>Schedule of the experimental protocol for selective breeding and behavioral testing.</p

Body temperature parameters in undisturbed circumstances during light and dark phases.

<p>The mean values of BT minimum (A), BT maximum (B), BT amplitudes (C), and the mean of changes in BT between two consecutive data points (D). * p <0.05 between groups; # p <0.05 between the day cycles; x p <0.05 between the BT decreases and increases. Data are presented as means ± SEM.</p

Poincaré plot analysis of body temperature in undisturbed circumstances during light and dark phases.

<p>Changes in SD1 (A) and SD2 (B). * p <0.05 between groups; # p <0.05 between the day cycles. Data are presented as means ± SEM.</p

A sample Poincaré plot analysis of temperature time series derived from a 12-h recording during dark phase from a control rat.

<p>The dashed line is the identity line; all points on this line correspond to two neighboring temperatures with equal values; all points above this line correspond to BT increases (BT_n+1>BT_n); all points below this line correspond to BT reductions (BT_n+1n). BT_n: BT of the current value, BT_n+1: BT of the next value. SD1: the standard deviation quantifying the dispersion of points in the Poincaré plot across the identity line. SD2 represents the dispersion along the identity line.</p

Motor activity parameters in undisturbed circumstances during light and dark phases.

<p>Mean AL (activity level; A), MI (movement index; B), RMI (relative movement index; C), PN (phase number; D), PL (phase length; E) with duration of uninterrupted immobility (DI) or active (DA) period. * p<0.05 between groups; # <0.05 between the day cycles; x p <0.05 between the DI and DA. Data are presented as means ± SEM.</p

The short- and long-term asymmetries of body temperature.

<p>The number of cases (N) have C1d > C1i, or C2d < C2i, and the degree of the relative contribution of decreases (C1d) or increases (C2i) to short- and long-term asymmetry, respectively.</p><p>* Significant degree of asymmetry;</p><p>^# p<0.05 compared to control group;</p><p>⁺ p<0.05 compared to light phase.</p><p>The short- and long-term asymmetries of body temperature.</p