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NMDA receptor antagonism impairs reversal learning in developing rats.
Kathryn K Chadman1, Deborah J Watson, Mark E Stanton
1Department of Psychology, University of Delaware, Newark, DE 19716, USA.
Behavioral Neuroscience
|October 4, 2006
Summary
Dizocilpine maleate (MK-801), an N-methyl-D-aspartate (NMDA) receptor antagonist, selectively impairs reversal learning in developing rats. This effect on cognitive flexibility was observed across various developmental stages tested.
Area of Science:
- Neuroscience
- Developmental Psychology
- Pharmacology
Background:
- N-methyl-D-aspartate (NMDA) receptors play a critical role in synaptic plasticity and learning.
- Understanding the developmental trajectory of cognitive functions, such as reversal learning, is crucial for identifying critical periods of vulnerability.
- NMDA receptor antagonists are tools used to probe the function of these receptors in various cognitive processes.
Purpose of the Study:
- To investigate the impact of dizocilpine maleate (MK-801), a noncompetitive NMDA receptor antagonist, on spatial discrimination and reversal learning during development.
- To determine if NMDA receptor antagonism affects acquisition and/or reversal learning differently.
- To assess age-related differences in sensitivity to MK-801's effects on learning in young rats.
Main Methods:
- Rats were administered varying doses of MK-801 (0.03-0.18 mg/kg) via intraperitoneal injection.
- Behavioral testing involved spatial discrimination and reversal learning tasks in a T-maze.
- Drug administration occurred before acquisition, before reversal, or only during reversal across different experimental conditions.
- Experiments were conducted on postnatal days (PND) 21, 26, and 30.
Main Results:
- Doses of 0.06 mg/kg and 0.10 mg/kg of MK-801 selectively impaired reversal learning, while 0.18 mg/kg broadly impaired performance.
- The selective impairment of reversal learning was confirmed in state-dependent learning and sensitization experiments.
- Spatial reversal learning demonstrated higher sensitivity to NMDA-receptor antagonism compared to initial acquisition.
- No significant age-related differences in MK-801 sensitivity were observed between PND 21 and 30.
Conclusions:
- NMDA receptor antagonism, specifically by MK-801, has a selective detrimental effect on cognitive flexibility, particularly reversal learning, during development.
- Reversal learning is more vulnerable to NMDA receptor blockade than the initial learning of a task.
- The developing brain's sensitivity to NMDA receptor antagonism regarding reversal learning does not significantly change between PND 21 and 30.
