Comparative Analysis of the Effects of Blockade of Striatal Metabotropic and Ionotropic Glutamate Receptors on Motor Behavior in Rats
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Chronic experiments on rats addressed the effects of blockade of NMDA and metabotropic glutamate receptors in the neostriatum on conditioned reflex avoidance (in a shuttle box) and spontaneous (in an open field) behavior. Glutamate receptor antagonists were given bilaterally into the neostriatum, in some experiments with the GABAA receptor antagonist picrotoxin (2 μg), which impairs execution of conditioned reflex skills and produces choreomyoclonic hyperkinesia. The most effective agent in preventing the adverse effects of picrotoxin on behavior was the type 5 metabotropic receptor antagonist MTEP (3 μg), which when given into the neostriatum without picrotoxin had no effect on measures of avoidance behavior and did not alter the level of spontaneous motor activity. In contrast, the type 1 metabotropic receptor antagonist EMQMCM (3 μg) degraded measures of normal motor behavior (indicative of a sedative effect) but did not prevent the actions of picrotoxin. The NMDA receptor antagonist MK-801 (dizocilpine, 1 and 5 μg) decreased picrotoxin-induced hyperkinesia but had only mild effects on its adverse influence on conditioned reflex activity; given alone into the striatum, it decreased normal motor activity. Considering the distributions of the study receptors on neostriatal neuron membranes, it is suggested that the most effective action, on type 5 glutamate receptors, may be linked with their involvement in supporting the activity of the “indirect” efferent pathway, the activity of which is impaired in the hyperkinetic type of dysfunction of the extrapyramidal motor system in Huntington’s chorea in humans.
Keywordsneostriatum motor behavior hyperkinesia dizocilpine picrotoxin glutamate receptors
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