Frontiers in Behavioral Neuroscience, 2015
Svoboda J, Stankova A, Entlerova M, Stuchlik A. Acute administration of MK-801 in an animal model of psychosis in rats interferes with cognitively demanding forms of behavioral flexibility on a rotating arena. Front Behav Neurosci. 2015; 9:75. IF = 3.3 (2014).
The inability to flexibly switch a strategy (i.e. deficit in cognitive flexibility) represents a typical symptom in schizophrenic patients. Although there are several validated tests of cognitive flexibility in rodent models of schizophrenia, they do not offer to test animals under more than two levels of cognitive load; furthermore they usually use only simple cues. In our study, we employed Carousel apparatus which easily allows for examining performance in several variously complex tasks of spatial memory. Rats were challenged with four conditions of spatial behavior flexibility, with increasing cognitive load. In each condition, we used a group of control rats (injected with saline) and two groups of rats with schizophrenia-like symptoms induced by acute administration of NMDA antagonist MK-801 (0.05 mg/kg or 0.1mg/kg). Application of MK-801 had no effect on the easiest type of flexibility, change in motoric response; it neither affected the ability to locate a place in new location (so called reversal) using the well-known set of spatial cues. However, application of MK-801 in the dose 0.1mg/kg significantly worsened cognitively most demanding challenge – to locate a place in new, previously ignored set of spatial cues (set-shifting). It had the effect on both types of set-shifting examined. These results suggest that inducing schizophrenia-like behavior compromise preferentially set-shifting type of cognitive flexibility. Therefore it may preferentially disrupt putative neural substrate of set-shifting – prefrontal cortex. In addition, the Carousel apparatus appeared to be a useful tool for assessing various levels of cognitive load during cognitive flexibility.
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