MK-801 impairs recognition memory in rhesus monkeys: comparison with cholinergic drugs

Both N-methyl-D-aspartate (NMDA) and cholinergic receptors are thought to participate in processes of learning and memory. The effects of the noncompetitive NMDA antagonist ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine) MK-801 on recognition memory in rhesus monkeys performing a computer-automated version of delayed nonmatching-to-sample DNMS were compared to those of the cholinergic compounds physostigmine and scopolamine. In the sample phase of the test, 20 symbols were presented sequentially every 30 sec on a color monitor fitted with a touch-sensitive screen. These symbols were then presented again in the same order as before, but each symbol was now paired with a different novel symbol. A monkey was rewarded with a food pellet if it touched the symbol in the sample phase and the previously unseen symbol in the choice phase. Physostigmine (3.2, 10 and 32 micrograms/kg), scopolamine (3.2, 10, 17.8 and 32 micrograms/kg) or MK-801 (3.2, 10 and 32 micrograms/kg) was injected i.m. 20, 20 and 30 min before testing, respectively. The highest doses of both MK-801 and scopolamine significantly impaired performance. In addition, scopolamine, but not MK-801, prolonged response latency, whereas MK-801, but not scopolamine, increased response bias. Physostigmine produced a small but significant increase in correct responses at the intermediate dose, but not at the highest dose. These results suggest that both the glutamatergic and the cholinergic systems participate in visual recognition memory in monkeys, though probably by different mechanisms.