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Learning impairments induced by glutamate blockade using dizocilpine (MK-801) in monkeys
J A Harder1, A A Aboobaker, T C Hodgetts
1MRC Comparative Cognition Team, Department of Experimental Psychology, Cambridge.
British Journal of Pharmacology
|December 10, 1998
Summary
Dizocilpine (MK-801) impairs specific learning tasks in marmosets without causing significant motor deficits. This highlights the role of glutamatergic blockade in cognitive decline, relevant to neurodegenerative diseases like Alzheimer's.
Area of Science:
- Neuroscience
- Primate Cognition
- Pharmacology
Background:
- Glutamatergic neurotransmission is crucial for learning and memory.
- Dysfunction in glutamatergic systems is implicated in neurodegenerative diseases.
- Non-human primates offer valuable models for studying complex cognitive processes.
Purpose of the Study:
- To investigate the effects of dizocilpine (MK-801), a glutamate receptor antagonist, on learning and memory in marmosets.
- To determine if cognitive deficits induced by dizocilpine are separable from motor side effects.
- To explore the relevance of these findings to cognitive decline in neurodegenerative conditions.
Main Methods:
- Marmosets were tested on visual and visuo-spatial discrimination tasks using the Wisconsin General Test Apparatus.
- Acquisition and reversal learning were assessed.
- Motor effects were evaluated through home cage observations, automated locomotor monitoring, and subjective counting of abnormal movements.
Main Results:
- Dizocilpine impaired the acquisition of visuo-spatial tasks and perceptually difficult visual discrimination tasks.
- Simple visual discrimination and its reversal were not significantly affected.
- Motor incoordination was observed only at a high dose, exceeding that used for cognitive testing.
Conclusions:
- Dizocilpine induces specific cognitive deficits in marmosets at doses that do not cause significant motor impairment.
- This study demonstrates a link between glutamatergic blockade and cognitive deficits in primates.
- Findings support the utility of this model for understanding cognitive decline in neurodegenerative diseases, particularly Alzheimer's disease.