Differential effects of two NMDA receptor antagonists on cognitive-behavioral development in nonhuman primates

The present experiment examined effects of chronic exposure to remacemide ( an N-methyl-D-aspartate [NMDA] antagonist which also blocks fast sodium cha nnels) or MK-801 (which blocks NMDA receptors, exclusively) on teaming and motivation in young rhesus monkeys. Remacemide (20 or 50 mg/kg/day) or MK-8 01 (0.1 or 1.0 mg/kg/day) was administered every day to separate groups of animals via orogastric gavage for up to 2 years. Immediately prior to dosin g, 5 days per week (M-F), throughout the 2-year dosing period, an increment al repeated acquisition (IRA) task was used to assess learning and a progre ssive ratio (PR) task was used to assess motivation. The results indicate a n effect of 50 mg/kg/day remacemide to impair learning (IRA) which persiste d even after drug treatment was discontinued. MK-801 had no effect on teami ng but transiently increased motivation. Because the effects of remacemide occurred independently of changes in motivation or response rates, they are likely due to specific cognitive impairments and are not due to an inabili ty of subjects to fulfill the motoric requirements of the task. The fact th at MK-801 did not alter learning suggests that NMDA antagonism alone may be insufficient to produce learning deficits in young monkeys and that such d eficits may rely on the ancillary blockade of fast sodium channels. (C) 200 1 Elsevier Science Inc. All rights reserved.