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Early NMDA receptor blockade impairs defensive behavior and increases cell proliferation in the dentate gyrus of
1Laboratory of Neuroendocrinology, Rockefeller University. goulde@princeton.edu
Insights
Early N-methyl-D-aspartate (NMDA) receptor blockade in rat pups impaired freezing behavior and increased dentate gyrus cell production. This suggests an inverse relationship between NMDA receptor antagonist exposure and defensive responses.
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Behavioral Neuroscience
Background:
- The N-methyl-D-aspartate (NMDA) receptor plays a critical role in synaptic plasticity and neuronal development.
- Understanding the impact of early-life NMDA receptor modulation on defensive behaviors and neurogenesis is crucial for developmental neuroscience.
Purpose of the Study:
- To investigate if early N-methyl-D-aspartate (NMDA) receptor blockade affects defensive behavior in rat pups.
- To determine the relationship between defensive behavior and granule cell production in the dentate gyrus following NMDA receptor blockade.
Main Methods:
- Rat pups were administered varying doses of the NMDA receptor antagonist CGP 43487 on postnatal day 5.
- Behavioral responses, specifically freezing, were assessed after exposure to a predator stimulus on postnatal days 13, 20, and 30.
- Neurogenesis was quantified by measuring (3)H-thymidine-labeled cells in the dentate gyrus.
Main Results:
- A dose-dependent impairment in freezing behavior was observed in rat pups treated with the NMDA receptor antagonist on postnatal days 13 and 20, but not 30.
- NMDA receptor antagonist treatment resulted in a dose-dependent increase in the number of (3)H-thymidine-labeled cells in the dentate gyrus.
- These findings indicate an inverse correlation between cell proliferation in the dentate gyrus and freezing behavior.
Conclusions:
- Early-life NMDA receptor blockade significantly impairs defensive freezing behavior in a time- and dose-dependent manner.
- NMDA receptor antagonism promotes neurogenesis in the dentate gyrus of developing rats.
- An inverse relationship exists between NMDA receptor-mediated neurogenesis and the development of defensive behaviors.
Abstract:
These studies were conducted to determine whether (a) early N-methyl-D-aspartate (NMDA) receptor blockade impairs defensive behavior and (b) a relationship exists between defensive behavior and the production of granule cells in the dentate gyrus. Rat pups were treated with different doses of the NMDA receptor antagonist CGP 43487 on postnatal day (P) 5, and their behavior was observed following exposure to an unfamiliar adult male rat, a potential predator, on P13, P20, and P30. A dose-dependent impairment in freezing behavior was observed in rat pups treated with NMDA receptor antagonist on P13, P20, but not P30. Moreover, a dose-dependent increase in the number of (3)H-thymidine-labeled cells in the dentate gyrus was detected following CGP 43487 treatment, suggesting that an inverse relationship exists between cell proliferation and freezing behavior in rat pups following NMDA receptor blockade.