Systemic administration of MK-801, a non-competitive NMDA-receptor antagonist, elicits a behavioural deficit of rats in the Active Allothetic Place Avoidance (AAPA) task irrespectively of their intact spatial pretraining

Spatial orientation is considered to be an animal model of human cognitive functions. Efficient navigation is believed to require a brain representation of the environment. The role of NMDA-receptor-dependent neurotransmission in encoding spatial representations has been intensively studied; however, its involvement in organizing spatial information into neural representations is poorly understood. We tested the effect of NMDA-receptor blockade on the performance of rats in Active Allothetic Place Avoidance (AAPA), a cognitive task which requires rats to separate two conflicting spatial reference frames (room and arena frames), when only the room frame is relevant for solution of the task. The NMDA-receptor blockade was achieved by systemic administration of either 0.15 mg/kg or 0.2 mg/kg of dizocilpine (MK-801), a non-competitive NMDA-receptor antagonist. Two distinct AAPA setups located in different rooms were used. The rooms had different layouts of robust extramaze landmarks. Intact rats were trained in the upstairs arena and, subsequently, they received saline or MK-801 and their performance was tested (reinforced retention). Re-acquisition of AAPA task in the downstairs room was then tested under saline or MK-801. MK-801 at the dose of 0.2 mg/kg was found to disrupt the reinforced retention of the AAPA. Re-acquisition of AAPA in the novel environment was impaired by both doses of MK-801. Taken together, administration of MK-801 causes an orientation deficit in the AAPA task irrespectively of the rats' prior intact pretraining. These results support the hypothesis that NMDA-receptors play a pivotal role in cognitive processes.