Maturation of locomotor and Fos responses to the NMDA antagonists, PCP andMK-801

Antagonists at the N-methyl-D-aspartate (NMDA)-type glutamate receptor, suc h as phencyclidine (PCP) and dizocilpine (MK-801), are well-known to evoke increases in locomotor activity in adult rats and mice. However, little is known about the effects of NMDA antagonists on locomotor activity as a func tion of development. The present study examined locomotor responses to PCP or MK-801 in male rats of varying ages and found that prepubertal rats were more sensitive to the locomotor-elevating effects of PCP (1.5 mg/kg and 3. 0 mg/kg, s.c.) than were adults. Locomotor responses to MK-801 (0.1 and 0.2 mg/kg, s.c.) were not dependent on age. The age-dependent response to PCP may be related to developmental events in the motor cortex, since more Fos- immunoreactive neurons were observed in the motor cortex of prepubertal ani mals after PCP administration relative to adult animals. An opposite patter n of age-dependent Fos responses was observed in the posterior retrosplenia l cortex. The results suggest that locomotor responses to NMDA antagonists can be influenced in an age- and drug-dependent manner and that maturationa l events in the motor cortex may modify responses to PCP. (C) 2000 Publishe d by Elsevier Science B.V. All rights reserved.