Abstract
We infused--for four weeks--a selective antagonist of the NMDA receptor, MK-801, into the subthalamic nucleus of rats bearing an evolving nigrostriatal lesion. The aim was to block the subthalamic overactivity resulting from the dopaminergic striatal denervation. The nigrostriatal lesion caused metabolic activation--increased activity of the mitochondrial enzyme succinate dehydrogenase--of basal ganglia nuclei, ipsilaterally to the lesion, along with contralateral rotational behavior. These phenomena were effectively counteracted by the blockade of glutamatergic transmission at the subthalamic level. Pharmacological manipulation of the STN, through selective drugs capable of modulating glutamatergic transmission, may therefore represent a valuable tool for the treatment of PD.
MeSH terms
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Amphetamine / pharmacology
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Animals
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Dizocilpine Maleate / pharmacology
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Energy Metabolism / drug effects
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Energy Metabolism / physiology
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Excitatory Amino Acid Antagonists / pharmacology*
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Functional Laterality / drug effects
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Functional Laterality / physiology
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Glutamic Acid / metabolism
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Male
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Motor Activity / drug effects
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Motor Activity / physiology
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Neostriatum / drug effects
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Neostriatum / metabolism*
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Neostriatum / physiopathology
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Neural Pathways / drug effects
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Neural Pathways / metabolism*
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Neural Pathways / physiopathology
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Neurons / drug effects
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Neurons / metabolism*
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Oxidopamine / pharmacology
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Parkinsonian Disorders / drug therapy*
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Parkinsonian Disorders / metabolism
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Parkinsonian Disorders / physiopathology
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Rats
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Rats, Sprague-Dawley
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Substantia Nigra / drug effects
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Substantia Nigra / metabolism*
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Substantia Nigra / physiopathology
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Subthalamic Nucleus / drug effects
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Subthalamic Nucleus / metabolism*
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Subthalamic Nucleus / physiopathology
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Succinate Dehydrogenase / metabolism
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Sympatholytics / pharmacology
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology
Substances
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Excitatory Amino Acid Antagonists
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Sympatholytics
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Glutamic Acid
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Dizocilpine Maleate
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Oxidopamine
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Amphetamine
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Succinate Dehydrogenase