THE NMDA ANTAGONIST MK-801 CAN IMPAIR ATTENTION TO EXTEROCEPTIVE STIMULI

Using a modified open-field method, we assessed the effects of MK-801 (0.01 to 0.3 mg/kg) on locomotion and on attention to a stimulus object located in a computer-generated central zone (CZ). The CZ comprised 1/9 of the open-field floor area and was monitored independently from the rest of the area. Intermittently, a 4 x 4 x 2 cm block was placed in the CZ. In 10-min trials, non-drug tests showed that the presence of the stimulus object repeatedly and consistently increased the rats' visit duration in the CZ as compared with tests when the object was absent. Locomotor activity and entries to the CZ were unaffected by the object. MK-801 induced dose dependent hyperlocomotion and increased CZ entries and, most important, a dose dependent decrease in the animal's response to the stimulus object in the CZ. The present investigation suggests that MK-801 impacts upon two major functions; (a) a blockade of processing of attentional information from the external world and (b) activation of locomotor response systems. These findings are consistent with the hypothesis that blockade of glutamate neurotransmission by MK-801 impairs the flow of information from the external world to response mechanisms in the striatum. The present study also suggests that MK-801's potential as a therapeutic agent for motoric activation in the treatment for Parkinson's disease would be contraindicated by its disruptive influence upon attention processing functions.