Linked Life Data

11080200

Source:http://linkedlifedata.com/resource/pubmed/id/11080200

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2000-11-20
pubmed:abstractText
The endogenous cannabinoid anandamide has been reported to produce well-defined behavioral tolerance, but studies on the possible mechanisms underlying this process are few and often contradictory. The present study was designed to survey the cellular events involved in anandamide tolerance, in terms of the effects on receptor number, coupling with G proteins, and activation of the cyclic AMP (cAMP) cascade. Chronic treatment of rats with anandamide (20 mg/kg i.p. for 15 days) resulted in behavioral tolerance without any change in cannabinoid receptor binding in the brain regions studied (striatum, cortex, hippocampus, and cerebellum), suggesting that receptor down-regulation was not involved in the development of anandamide behavioral tolerance. In contrast, prolonged exposure to anandamide significantly reduced agonist-stimulated guanosine 5'-O:-(3-[(35)S]thiotriphosphate) binding in the same areas, with losses of >50%, suggesting that receptor desensitization may be part of the molecular mechanism underlying this tolerance. Finally, concerning the cAMP cascade-the most well-known intracellular signaling pathways activated by CB(1) receptors-in the brain regions from rats tolerant to anandamide, we found no alteration in cAMP levels or in protein kinase A activity. We propose that anandamide, unlike Delta(9)-tetrahydrocannabinol and other cannabinoids, does not alter the receptor system at multiple levels but that desensitization of the CB(1) receptor might account for behavioral tolerance to the drug.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
75
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2478-84
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11080200-Animals, pubmed-meshheading:11080200-Arachidonic Acid, pubmed-meshheading:11080200-Arachidonic Acids, pubmed-meshheading:11080200-Behavior, Animal, pubmed-meshheading:11080200-Binding, Competitive, pubmed-meshheading:11080200-Body Weight, pubmed-meshheading:11080200-Brain, pubmed-meshheading:11080200-Cannabinoids, pubmed-meshheading:11080200-Cerebellum, pubmed-meshheading:11080200-Cerebral Cortex, pubmed-meshheading:11080200-Corpus Striatum, pubmed-meshheading:11080200-Dose-Response Relationship, Drug, pubmed-meshheading:11080200-Down-Regulation, pubmed-meshheading:11080200-Drug Tolerance, pubmed-meshheading:11080200-GTP-Binding Proteins, pubmed-meshheading:11080200-Guanosine 5'-O-(3-Thiotriphosphate), pubmed-meshheading:11080200-Hippocampus, pubmed-meshheading:11080200-Male, pubmed-meshheading:11080200-Polyunsaturated Alkamides, pubmed-meshheading:11080200-Rats, pubmed-meshheading:11080200-Rats, Sprague-Dawley, pubmed-meshheading:11080200-Receptors, Cannabinoid, pubmed-meshheading:11080200-Receptors, Drug, pubmed-meshheading:11080200-Signal Transduction
pubmed:year
2000
pubmed:articleTitle
Loss of cannabinoid-stimulated guanosine 5'-O-(3-[(35)S]Thiotriphosphate) binding without receptor down-regulation in brain regions of anandamide-tolerant rats.
pubmed:affiliation
Department of Pharmacology, Chemotherapy, and Toxicology, University of Milan, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't