Effects of neonatal NMDA-subtype glutamate receptor blockade on behavior of adult male rats

Abstract

Introduction. Cognitive impairments are important components of the clinical picture of many neuropsychiatric disorders, and are in dire need of evidence-based pharmacotherapeutic approaches.The objective was to test a model of delayed cognitive impairments due to neonatal administration of NMDA receptor antagonists (7th, 9 th, and 11 th days of life).Methods and materials. Male Wistar rats were administered with phencyclidine, 10 mg/kg (Experiment 1), or (+)MK-801, 1 mg/kg (Experiment 2); then «2-choice serial reaction time task», or «reinforcement learning task based on response patterning under interval schedules of reinforcement» in the same adult rats were performed.Results. Experiment 1: rats after neonatal NMDA-blockade performed operant tasks more accurately and made fewer missed attempts as compared to control. Experiment 2: switching to another schedule of reinforcement increased the pause after reinforced responses in both groups; in the experimental group, the duration of the post-reinforcement pause was shorter.Conclusion. Neonatal NMDA receptor blockade affects inhibitory control and attention to sensory stimuli, which manifests, respectively, as increased impulsivity and hyperfocusing in limited-choice conditions.