Perinatal, subchronic NMDA receptor antagonism attenuates behavior from childhood to adulthood in rats

The NMDA (N-methyl-D-aspartate) receptor system is the major excitatory transmitter system in the central nervous and plays a crucial role in the pathology of psychiatric disorders. We therefore tested the effects of a perinatal, subchronic NMDA antagonism on the anxiety, locomotor and exploratory behavior of rats throughout their life beginning at the age of 30 days until 180 days. NMDA depletion profoundly reduced locomotor activity as indicated by a decreased total distance moved and reduced velocity in the Elevated Plus Maze and the Open Field Maze. Changes in the total time spent in the different zones of the Mazes are interpretated as a reduction of anxiety. For almost all behavioral parameters, NMDA depletion extinguished age-related changes as found in vehicle-treated rats. Taken together, attenuating the perinatal development of the NMDA receptor within the central nervous system significantly affects anxiety and locomotor behavior of rats during a long period of the subsequent life.