Two learning tasks provide evidence for disrupted behavioural flexibility in an animal model of schizophrenia-like behaviour induced by acute MK-801: a dose-response study.

ABSTRACT

Schizophrenia is a chronic and devastating illness. Exact causes of the disease remain elusive; however, neurodevelopmental changes in the brain glutamate system are recognized to play an important role. Several animal models of the disease are induced by a systemic blockade of N-methyl-d-aspartate (NMDA) receptors. This study examined the animal model of schizophrenia-like behaviours induced by acute treatment with MK-801, a non-competitive NMDA-receptor antagonist. Behavioural flexibility is an ability to adapt to the changes in environment, and schizophrenia is often accompanied by its decrease. The study tested the effect of MK-801 on behavioural flexibility in an active place avoidance task and the Morris water maze (MWM). Flexibility was tested under reversal conditions, i.e., after changing the location of the target. Each spatial task addressed different functions; continuous coordinate-frame segregation was present in the active place avoidance and precise place representation in the MWM. Results showed that reversal was altered in both tasks by MK-801 at doses of 0.10-0.15 mgkg(-1). Some impairment was observed in the active place avoidance task at 0.08 mgkg(-1). Swimming towards a visible platform was impaired only by the highest dose (0.15 mgkg(-1)). The results demonstrate that a significant impairment of behavioural flexibility accompanies this acute animal model of schizophrenia-like behaviours, and that active place avoidance had higher sensitivity for such deficits than the MWM. This suggests the usefulness of the reversal paradigm in both tasks for examining novel drugs with antipsychotic and procognitive actions.