ALTERED NMDA SENSITIVITY AND LEARNING FOLLOWING CHRONIC DEVELOPMENTALNMDA ANTAGONISM

We have previously shown that chronic developmental administration of N-methyl-D-aspartate (NMDA) antagonists reduces synaptic development; however, on withdrawal from NMDA antagonism, there is a rebound period during which synaptogenesis exceeds control levels. The current resea rch was undertaken to explore this period of withdrawal, using the non competitive antagonist phencyclidine (PCP), examining 2 behavioral mea sures in which the NMDA receptor is implicated: 1. NMDA-induced seizur es, and 2. learning and memory in the Morris water maze. Using a proto col identical to that previously used to examine synaptic development, male Long-Evans rats were given 1 daily SC injection of either 10 mg/ kg PCP or its physiological saline vehicle for a period of 15 days, be ginning on postnatal Day 5 (P5) and ending on P20. Animals were then a ssessed for either sensitivity to NMDA-induced seizures on P21, P26, P 36, or P56, or they were assessed for their acquisition performance an d initial heading in the Morris water maze on P23, P26, P30, P38, and P75. Chronic treatment with PCP resulted in greater behavioral ratings of seizure activity after NMDA administration, observed 1(P21), 5 (P2 6), and 15 (P36) days after the last injection of PCP, indicating incr eased sensitivity of the NMDA receptor/channel complex during this per iod after withdrawal from developmental NMDA antagonism. PCP-treated a nimals also required significantly more trials to reach criterion in t he Morris water maze on P23, P26, and P30, and displayed significantly less accurate initial swim headings on all test days. The results are discussed in terms of the role of the NMDA receptor-channel complex i n development and learning/memory processes. (C) 1997 Elsevier Science Inc.