Effects of early postnatal MK-801 treatment on behavioral properties in rats: Differences according to treatment schedule

Abstract

It has been proposed that animals administered early postnatal NMDA (N-methyl-d-aspartate) glutamate receptor antagonists represent a model of schizophrenia; however, drug treatment schedules remain quite different among these animal studies. In this study, we compared the behavioral effects of long-term (14-day) and short-term (5-day) early postnatal treatment of the NMDA receptor antagonist MK-801 (dizocilpine; 5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine). In addition, different drug treatment periods were applied to the short-term treatment study in order to determine the critical developmental period of drug effects. For experiment 1, rats were treated with MK-801 (0.2 or 0.4 mg/kg, twice daily) during postnatal days (PNDs) 7–20. For experiment 2, MK-801 (0.2 mg/kg, twice daily) was administered during the periods of PNDs 7–11, 12–16, and 17–21. In adulthood, several behavioral tests, including prepulse inhibition, open-field, and spontaneous alternation tests, were performed in experiments 1 and 2. The delayed nonmatching-to-position task was also conducted in experiment 2 on separate rats treated for 5 days in the same manner. Our results indicated that the 14-day MK-801 treatment inhibited the prepulse inhibition and decreased immobility in the forced-swim test, whereas the 5-day MK-801 treatment induced only slight behavioral effects. Collectively, our findings suggest that long-term early postnatal treatment with an NMDA receptor antagonist may be detrimental to some behavioral functions, such as sensorimotor gating and stress coping; however, treatment for longer periods is needed to elicit detrimental effects.