LEARNING IMPAIRMENTS INDUCED BY GLUTAMATE BLOCKADE USING DIZOCILPINE (MK-801) IN MONKEYS

1 This study investigated the effects of dizocilpine (MK-801) on learn ing ability in a non-human primate. Acquisition and reversal learning of visual discrimination tasks and acquisition of visuo-spatial discri mination tasks were assessed in marmosets using the Wisconsin General Test Apparatus. Dizocilpine impaired acquisition of visuo-spatial (con ditional) tasks requiring spatial responses to coloured objects, and p erceptually difficult visual discrimination tasks in which stimulus ob jects are painted black. Dizocilpine did not, however, impair either a cquisition or reversal of a simple visual discrimination task using ea sily discriminated, coloured objects. 2 Motor effects of dizocilpine t reatment, which have been seen in other primates, were examined by obs ervation of the marmosets in their home cages, using both an automated locomotor activity monitor and 'blind', subjective counting of the nu mber of abnormal movements in a given time period. Locomotor activity, assessed using the automated monitor, was not significantly affected at any of the doses tested. Incoordination, assessed by human observat ion of abnormal movements, was significantly increased only at a dose of 30 mu g kg(-1) i.m., which was twice the highest dose used to asses s the effects of dizocilpine on cognition. 3 We have, therefore, found an effect of dizocilpine on acquisition and reversal of some types of cognitive task, at a dose which does not cause significant motor effe cts. This demonstration of a cognitive deficit associated with glutama tergic blockade in a primate may be useful in understanding the contri bution of glutamatergic dysfunction to cognitive decline in neurodegen erative disease, especially Alzheimer's disease.