Acute behavioral toxicity of MK-801 and phencyclidine: effects on rhesus monkey performance in an operant test...

Monkey performance of operant tasks was used to model several brain functions and monitor the acute effects of MK-801 and phencyclidine (PCP). MK-801 is a relatively selective N-methyl-D-aspartate (NMDA) receptor antagonist, while PCP is an NMDA antagonist that is also active at sigma opiate receptors. A comparison of these drugs' effects may indicate the relative importance of certain neurotransmitter receptor systems for specific behaviors. Learning and time perception behaviors are more sensitive (affected at lower doses) to the disruptive effects of MK-801 than are behaviors that model short-term memory, motivation, and color and position discrimination. Such selective disruption was not obtained for PCP: learning, short-term memory and attention, time perception, and motivation tasks are all equally sensitive to disruption. These findings suggest that specific brain functions are differentially affected by modulation of the NMDA and sigma opiate systems.