MK801 IMPAIRS ACQUISITION AND EXPRESSION OF CONDITIONED-RESPONSES IN THE RABBIT NICTITATING-MEMBRANE PREPARATION

MK801 is a noncompetitive antagonist to N-methyl-D-aspartate (NMDA) re ceptors. MK801 (0.1 mg/kg IV) was given to rabbits during classical co nditioning of their nictitating membrane response. Administration of M K801 before each braining session impaired acquisition of a conditione d response (CR). When MK801 administration was suspended, responding r emained at a low level. Control animals were given either MK801 after each training session (Experiment 1) or saline before each session (Ex periment 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 form er level when the original control condition was reinstated. In all th e animals, tests for motor deficits caused by MK801 proved negative; t he magnitude of the UR was not influenced by MK801 at either the begin ning or end of training. In conclusion, it appears that MK801 impairs both the formation of associative linkages and the performance of esta blished CRs. A reduction in CS salience caused by MK801 is the most pa rsimonious explanation of the data. There is a more complex, two-facto r alternative that contends that MK801 directly hindered associative f ormation in the subjects trained with that drug and produced a state-d ependent generalization decrement in responding when introduced to the control subjects.