Abstract
Excitatory neuronal activity produces beneficial influences on neuronal survival under several circumstances. We show that cultivation of rat midbrain slices in the presence of elevated extracellular Mg(2+) resulted in a marked decrease in the number of dopaminergic neurons. The effect was prominent when Mg(2+) was added to the medium during the first week of cultivation. Chronic treatment with antagonists of N-methyl-D-aspartate receptors such as 2-amino-5-phosphonovaleric acid, MK-801 and ifenprodil also resulted in a marked loss of dopaminergic neurons, whereas nicotinic receptor antagonists showed no effect. The effect of MK-801 was abolished by chronic depolarization by elevated extracellular K(+), or by application of forskolin or dibutyryl cyclic AMP. Thus, tonic activation of N-methyl-D-aspartate receptors driven by neuronal activity may play an important role in the maintenance of dopaminergic neurons.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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2-Amino-5-phosphonovalerate / pharmacology
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Animals
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Animals, Newborn
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Colforsin / pharmacology
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Culture Techniques
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Dizocilpine Maleate / pharmacology
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Dopamine / metabolism*
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Dose-Response Relationship, Drug
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Drug Interactions
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Excitatory Amino Acid Antagonists / pharmacology
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Immunohistochemistry
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Magnesium / pharmacology
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Mesencephalon / drug effects
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Mesencephalon / metabolism*
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Neurons / drug effects
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Neurons / metabolism*
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Piperidines / pharmacology
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Potassium / pharmacology
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Rats
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Rats, Wistar
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Receptors, N-Methyl-D-Aspartate / drug effects
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Receptors, N-Methyl-D-Aspartate / metabolism*
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Sodium / pharmacology
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Time Factors
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Tyrosine 3-Monooxygenase / metabolism
Substances
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Excitatory Amino Acid Antagonists
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Piperidines
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Receptors, N-Methyl-D-Aspartate
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Colforsin
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Dizocilpine Maleate
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2-Amino-5-phosphonovalerate
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Sodium
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Tyrosine 3-Monooxygenase
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Magnesium
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ifenprodil
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Potassium
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Dopamine