Modulatory treatment of NMDA receptors in neonatal rats affects cognitive behavior in adult age.
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.
Wangen
K
K
Norwegian Defence Research Establishment, Division for Environmental Toxicology, Kjeller, Norway.
Myhrer
T
T
Moldstad
J N
JN
Iversen
E G
EG
Fonnum
F
F
D000818:Animals; D000831:Animals, Newborn; D002531:Cerebellum / Q000187:drug effects* / Q000254:growth & development; D002540:Cerebral Cortex / Q000187:drug effects* / Q000254:growth & development; D003071:Cognition / Q000187:drug effects*; D003523:Cycloserine / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005106:Exploratory Behavior / Q000187:drug effects*; D008297:Male; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D013237:Stereoisomerism
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D011760:Pyrrolidinones; D016194:Receptors, N-Methyl-D-Aspartate; D003523:Cycloserine; C001369:1-hydroxy-3-amino-2-pyrrolidone