Abstract
Nitric oxide (NO) is a retrograde messenger involved in the processes of learning and memory. The role of the endothelial isoform of nitric oxide synthase (eNOS) in striatal synaptic plasticity was investigated in eNOS-deficient (eNOS(-/-)) and wild type (WT) mice. Tetanic stimulation of cortical afferents in WT mice evoked either long-term potentiation (LTP), or long-term depression (LTD) of cortico-striatal transmission. Both these plasticity related phenomena were NMDA-receptor-dependent; LTD was blocked by sulpiride, a dopamine D2-receptor antagonist. LTP occurrence in slices from eNOS(-/-) mice was significantly reduced when compared with WT mice. The NOS inhibitor NL-ARG reduced the occurrence of LTP and increased the occurrence of LTD in WT mice, resembling the balance of LTP/LTD in eNOS(-/-) mice. Impairment of NO-synthesis thus shifts striatal plasticity towards LTD. This indicates a possible involvement of eNOS from endothelia in neuronal modulation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cerebral Cortex / cytology
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Cerebral Cortex / enzymology*
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Cerebral Cortex / growth & development
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Dopamine Antagonists / pharmacology
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Dopamine D2 Receptor Antagonists
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Electric Stimulation
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Enzyme Inhibitors / pharmacology
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Excitatory Amino Acid Antagonists / pharmacology
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Female
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Learning / physiology
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Long-Term Potentiation / drug effects
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Long-Term Potentiation / physiology
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Long-Term Synaptic Depression / drug effects
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Long-Term Synaptic Depression / physiology
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Male
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Memory / physiology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Neostriatum / cytology
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Neostriatum / enzymology*
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Neostriatum / growth & development
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Neuronal Plasticity / physiology*
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Nitric Oxide / biosynthesis*
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Nitric Oxide Synthase / antagonists & inhibitors
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Nitric Oxide Synthase / deficiency*
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Nitric Oxide Synthase / genetics
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Receptors, Dopamine D2 / metabolism
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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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Synapses / enzymology*
Substances
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Dopamine Antagonists
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Dopamine D2 Receptor Antagonists
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Enzyme Inhibitors
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Excitatory Amino Acid Antagonists
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Receptors, Dopamine D2
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Receptors, N-Methyl-D-Aspartate
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Nitric Oxide
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Nitric Oxide Synthase