Source:http://linkedlifedata.com/resource/pubmed/id/20950413
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
2010-12-2
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pubmed:abstractText |
The contribution of nociceptin/orphanin FQ (N/OFQ) to reserpine-induced Parkinsonism was evaluated in mice. A battery of motor tests revealed that reserpine caused dose-dependent and long-lasting motor impairment. Endogenous N/OFQ sustained this response because N/OFQ peptide (NOP) receptor knockout (NOP(-/-) ) mice were less susceptible to the hypokinetic action of reserpine than wild-type (NOP(+/+) ) animals. Microdialysis revealed that reserpine elevated glutamate and reduced GABA levels in substantia nigra reticulata, and that resistance to reserpine in NOP(-/-) mice was accompanied by a milder increase in glutamate and lack of inhibition of GABA levels. To substantiate this genetic evidence, the NOP receptor antagonist 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-2H benzimidazol-2-one (J-113397) simultaneously reduced akinesia and nigral glutamate levels in reserpinized NOP(+/+) mice, being ineffective in NOP(-/-) mice. Moreover, repeated J-113397 administration in reserpinized mice resulted in faster recovery of baseline motor performance which was, however, accompanied by a loss of acute antiakinetic response. The short-term beneficial effect of J-113397 was paralleled by normalization of nigral glutamate levels, whereas loss of acute response was paralleled by loss of the ability of J-113397 to inhibit glutamate levels. We conclude that endogenous N/OFQ contributes to reserpine-induced Parkinsonism, and that sustained NOP receptor blockade produces short-term motor improvement accompanied by normalization of nigral glutamate release.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Benzimidazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Excitatory Amino Acids,
http://linkedlifedata.com/resource/pubmed/chemical/J 113397,
http://linkedlifedata.com/resource/pubmed/chemical/Opioid Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Piperidines,
http://linkedlifedata.com/resource/pubmed/chemical/Reserpine,
http://linkedlifedata.com/resource/pubmed/chemical/nociceptin
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1471-4159
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pubmed:author | |
pubmed:copyrightInfo |
© 2010 The Authors. Journal of Neurochemistry © 2010 International Society for Neurochemistry.
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pubmed:issnType |
Electronic
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pubmed:volume |
115
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1543-55
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pubmed:meshHeading |
pubmed-meshheading:20950413-Animals,
pubmed-meshheading:20950413-Benzimidazoles,
pubmed-meshheading:20950413-Dose-Response Relationship, Drug,
pubmed-meshheading:20950413-Excitatory Amino Acids,
pubmed-meshheading:20950413-Mice,
pubmed-meshheading:20950413-Mice, Knockout,
pubmed-meshheading:20950413-Motor Activity,
pubmed-meshheading:20950413-Opioid Peptides,
pubmed-meshheading:20950413-Parkinsonian Disorders,
pubmed-meshheading:20950413-Piperidines,
pubmed-meshheading:20950413-Reserpine
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pubmed:year |
2010
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pubmed:articleTitle |
Further evidence for an involvement of nociceptin/orphanin FQ in the pathophysiology of Parkinson's disease: a behavioral and neurochemical study in reserpinized mice.
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pubmed:affiliation |
Department of Experimental and Clinical Medicine, Section of Pharmacology, University of Ferrara, Ferrara, Italy.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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