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

Abstract

The rodent tasks with food rewards are useful methods to evaluate memory functions, including hole-board and corridor tests. The AMBITUS system (a square corridor with several food rewards), as a combination of these tests, was developed for the investigation of a variety of parameters associated with exploration and cognitive performance in rodents. Experiments were performed to characterize these behaviors in healthy rats and a new "schizophrenia-like" rat substrain with impaired learning ability to reveal the reliability in tests related to these functions.A square corridor was constructed with equally spaced sites along each wall (4 inside and 4 outside) resulting in 16 side-boxes for food rewards. Photocells at each box recorded the visits into the side-boxes (as exploratory activity), while the eating parameters were obtained from video records. The animals were exposed to two types of tasks repeatedly in two series: all (16) or only the inside (8) boxes (Task 1 or Task 2, respectively) were baited.Most of the rats acquired Task 1, and their performance improved by repetition, but the new substrain showed decreased exploration and learning capacity. The introduction of Task 2 caused prompt preference of the baited inner side-boxes, and gradually improved working and reference memory during the trials. The manual and automated scoring of the visits into the side-boxes showed significant (r=0.97) correlation.The results proved that healthy animals could perform the simple tasks in the square corridor after a few repetitions. The semi-automated AMBITUS system might be appropriate to detect cognitive flexibility after different manipulations, and it provides immediate, online assessment of exploratory behavior of a large number of animals within a short period of time, and it reduces the possibility of experimenter bias.

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.…”

“…A rectangular corridor was constructed of clear Plexiglas on black floor with an external diameter of 80 cm, width of 8 cm and height of 50 cm, where the rats could move around between the walls forward and backward [7] (Fig. 1A-B).…”

“…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]. Memory formation is one of the most important capabilities of the central nervous system, which requires the cooperation of various mental abilities depending on different systems within the brain [10,11].…”

“…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].…”

“…For detailed characterization of the exploratory activity and learning abilities of rodents, we constructed the AMBITUS system, a combination of the hole-board and corridor tests [7]. It has been proven that control, but not Wisket animals, can find most of the food rewards after a few trials.…”