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Modulatory treatment of NMDA receptors in neonatal rats affects cognitive behavior in adult age
K Wangen1, T Myhrer, J N Moldstad
1Norwegian Defence Research Establishment, Division for Environmental Toxicology, Kjeller, Norway.
Insights
Neonatal exposure to the NMDA receptor antagonist (+)-HA-966 impaired adult cognitive behavior in rats, reducing novelty preference and exploratory activity. Glutamatergic agonist D-cycloserine showed no cognitive effects.
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Cognitive Neuroscience
Background:
- The glutamatergic NMDA receptor plays a crucial role in neural development and cognitive function.
- Disruptions during critical developmental periods can lead to lasting cognitive impairments.
Purpose of the Study:
- To investigate the long-term effects of neonatal NMDA receptor modulation on cognitive functions in adult rats.
- To assess the impact of D-cycloserine (agonist) and (+/-)-HA-966 (antagonist) on adult behavior.
Main Methods:
- Rat pups were administered D-cycloserine or (+/-)-HA-966 daily during postnatal days 10-20.
- Adult rats were tested in a novelty exploration task to evaluate cognitive behavior.
- Experiment 2 specifically examined the effects of the (+)-enantiomer of HA-966.
Main Results:
- Neonatal D-cycloserine treatment did not affect cognitive function in adult rats.
- (+/-)-HA-966 and D-cycloserine at 10 mg/kg caused minor increases in locomotor activity.
- (+)-HA-966 treatment resulted in reduced novelty preference, decreased exploratory and locomotor activity, and increased grooming behavior in adulthood.
Conclusions:
- Neonatal administration of the NMDA receptor antagonist (+)-HA-966 can impair cognitive functions, specifically novelty seeking and exploration, in adult rats.
- The glutamatergic agonist D-cycloserine did not demonstrate significant long-term cognitive effects in this study.
- These findings highlight the critical role of NMDA receptor function during development for establishing normal cognitive abilities in adulthood.
Abstract:
The glutamatergic NMDA receptor is probably involved in establishing functional connections during development, and interference may promote or impair cognitive functions in adult age. In the present study, rat pups received one daily injection of the NMDA receptor partial agonist D-cycloserine in various concentrations (3, 10, 50 mg/kg), the NMDA receptor antagonist (+/-)-HA-966 (30 mg/kg), or saline throughout postnatal days 10-20 (Experiment 1). In Experiment 2, effects of the (+)-enantiomer of HA-966 were similarly examined. The rats were tested in a novelty task in adult age (postnatal days 98-112). The results from Experiment 1 show that injections of D-cycloserine in the concentration of 10 mg/kg or (+/-)-HA-966 caused a slight increase in locomotor activity only. The results from Experiment 2 show that (+)-HA-966-treated rats displayed reduced preference for novelty, a slight reduction in exploratory activity and locomotor behavior, and increased rate of grooming. These results suggest that neonatal treatment with (+)-HA-966 can impair cognitive behavior in adult life. It was not possible to record any effects on cognitive function after neonatal administration of the glutamatergic agonist D-cycloserine.