Source:http://linkedlifedata.com/resource/pubmed/id/10582605
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
1999-12-27
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pubmed:abstractText |
Chronic treatment of rats with delta9-tetrahydrocannabinol (delta9-THC) results in tolerance to its acute behavioral effects. In a previous study, 21-day delta9-THC treatment in rats decreased cannabinoid activation of G proteins in brain, as measured by in vitro autoradiography of guanosine-5'-O-(3-[35S]thiotriphosphate) ([35S]GTPgammaS) binding. The present study investigated the time course of changes in cannabinoid-stimulated [35S]GTPgammaS binding and cannabinoid receptor binding in both brain sections and membranes, following daily delta9-THC treatments for 3, 7, 14, and 21 days. Autoradiographic results showed time-dependent decreases in WIN 55212-2-stimulated [35S]GTPgammaS and [3H]WIN 55212-2 binding in cerebellum, hippocampus, caudate-putamen, and globus pallidus, with regional differences in the rate and magnitude of down-regulation and desensitization. Membrane binding assays in these regions showed qualitatively similar decreases in WIN 55212-2-stimulated [35S]GTPgammaS binding and cannabinoid receptor binding (using [3H]SR141716A), and demonstrated that decreases in ligand binding were due to decreases in maximal binding values, and not ligand affinities. These results demonstrated that chronic exposure to delta9-THC produced time-dependent and region-specific down-regulation and desensitization of brain cannabinoid receptors, which may represent underlying biochemical mechanisms of tolerance to cannabinoids.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Benzoxazines,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Guanosine 5'-O-(3-Thiotriphosphate),
http://linkedlifedata.com/resource/pubmed/chemical/Morpholines,
http://linkedlifedata.com/resource/pubmed/chemical/Naphthalenes,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cannabinoid,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Drug,
http://linkedlifedata.com/resource/pubmed/chemical/Tetrahydrocannabinol,
http://linkedlifedata.com/resource/pubmed/chemical/Win 55212-2
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0022-3042
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
73
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2447-59
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:10582605-Animals,
pubmed-meshheading:10582605-Benzoxazines,
pubmed-meshheading:10582605-Brain,
pubmed-meshheading:10582605-Cell Membrane,
pubmed-meshheading:10582605-Down-Regulation,
pubmed-meshheading:10582605-Drug Administration Schedule,
pubmed-meshheading:10582605-Drug Tolerance,
pubmed-meshheading:10582605-GTP-Binding Proteins,
pubmed-meshheading:10582605-Guanosine 5'-O-(3-Thiotriphosphate),
pubmed-meshheading:10582605-Morpholines,
pubmed-meshheading:10582605-Naphthalenes,
pubmed-meshheading:10582605-Rats,
pubmed-meshheading:10582605-Receptors, Cannabinoid,
pubmed-meshheading:10582605-Receptors, Drug,
pubmed-meshheading:10582605-Tetrahydrocannabinol
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pubmed:year |
1999
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pubmed:articleTitle |
Chronic delta9-tetrahydrocannabinol treatment produces a time-dependent loss of cannabinoid receptors and cannabinoid receptor-activated G proteins in rat brain.
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pubmed:affiliation |
Department of Physiology and Pharmacology, Center for the Neurobiological Investigation of Drug Abuse, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.
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