MK801 impairs acquisition and expression of conditioned responses in the rabbit nictitating membrane preparation

Abstract

MK801 is a noncompetitive antagonist to N-methyl-D-aspartate (NMDA) receptors. MK801 (0.1 mg/kg IV) was given to rabbits during classical conditioning of their nictitating membrane response. Administration of MK801 before each training session impaired acquisition of a conditioned response (CR). When MK801 administration was suspended, responding remained at a low level. Control animals were given either MK801 after each training session (Experiment 1) or saline before each session (Experiment 2). The control animals showed high levels of CR acquisition. When the control animals were given the MK801 before a session, they showed a large deficit in responding. Responding returned to its former level when the original control condition was reinstated. In all the animals, tests for motor deficits caused by MK801 proved negative; the magnitude of the UR was not influenced by MK801 at either the beginning or end of training. In conclusion, it appears that MK801 impairs both the formation of associative linkages and the performance of established CRs. A reduction in CS salience caused by MK801 is the most parsimonious explanation of the data. There is a more complex, two-factor alternative that contends that MK801 directly hindered associative formation in the subjects trained with that drug and produced a state-dependent generalization decrement in responding when introduced to the control subjects.