Linked Life Data

16079992

Source:http://linkedlifedata.com/resource/pubmed/id/16079992

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2005-10-19
pubmed:abstractText
The aim of this work was to study the mechanism of cross-modulation between cannabinoid and opioid systems for analgesia during acute and chronic exposure. Acute coadministration of ineffectual subanalgesic doses of the synthetic cannabinoid CP-55,940 (0.2 mg/kg i.p.) and morphine (2.5 mg/kg i.p.) resulted in significant antinociception. In chronic studies, a low dose of CP-55,940 (0.2 mg/kg, i.p.) that per se did not induce analgesia in naive animals produced a significant degree of antinociception in rats made tolerant to morphine, whereas in rats made tolerant to CP-55,940, morphine challenge did not produce any analgesic response. To identify the mechanism of these asymmetric interactions during chronic treatment, we investigated the functional activity of cannabinoid and mu opioid receptors and their effects on the cyclic AMP (cAMP) cascade. Autoradiographic-binding studies indicated a slight but significant reduction in cannabinoid receptor levels in the hippocampus and cerebellum of morphine-tolerant rats, whereas CP-55,940-stimulated [35S]GTPgammaS binding showed a significant decrease in receptor/G protein coupling in the limbic area. In CP-55,940 exposed rats, mu opioid receptor binding was significantly raised in the lateral thalamus and periaqueductal gray (PAG), with an increase in DAMGO-stimulated [35S]GTPgammaS binding in the nucleus accumbens. Finally, we tested the cAMP system's responsiveness to the cannabinoid and opioid in the striatum and dorsal mesencephalon. In vivo chronic morphine did not affect CP-55,940's ability to inhibit forskolin-stimulated cAMP production in vitro and actually induced sensitization in striatal membranes. In contrast, in vivo chronic CP-55,940 desensitized DAMGO's efficacy in inhibiting forskolin-stimulated cAMP production in vitro. The alterations to the cAMP system seem to mirror the behavioral responses, indicating that the two systems may interact at the postreceptor level. This might open up new therapeutic opportunities for relief of chronic pain through cannabinoid-opioid coadministration.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0033-3158
pubmed:author
pubmed:issnType
Print
pubmed:volume
182
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
527-36
pubmed:dateRevised
2007-7-6
pubmed:meshHeading
pubmed-meshheading:16079992-Animals, pubmed-meshheading:16079992-Area Under Curve, pubmed-meshheading:16079992-Behavior, Animal, pubmed-meshheading:16079992-Brain, pubmed-meshheading:16079992-Brain Chemistry, pubmed-meshheading:16079992-Cannabinoids, pubmed-meshheading:16079992-Cyclic AMP, pubmed-meshheading:16079992-Cyclohexanols, pubmed-meshheading:16079992-Dose-Response Relationship, Drug, pubmed-meshheading:16079992-Drug Administration Schedule, pubmed-meshheading:16079992-Drug Interactions, pubmed-meshheading:16079992-Enkephalin, Ala(2)-MePhe(4)-Gly(5)-, pubmed-meshheading:16079992-Guanosine 5'-O-(3-Thiotriphosphate), pubmed-meshheading:16079992-Male, pubmed-meshheading:16079992-Narcotics, pubmed-meshheading:16079992-Pain Measurement, pubmed-meshheading:16079992-Radioligand Assay, pubmed-meshheading:16079992-Rats, pubmed-meshheading:16079992-Rats, Sprague-Dawley, pubmed-meshheading:16079992-Receptors, Cannabinoid, pubmed-meshheading:16079992-Receptors, Opioid, pubmed-meshheading:16079992-Sulfur Isotopes, pubmed-meshheading:16079992-Tritium
pubmed:year
2005
pubmed:articleTitle
Molecular mechanisms involved in the asymmetric interaction between cannabinoid and opioid systems.
pubmed:affiliation
DBSF, Pharmacology Section and Neuroscience Center, University of Insubria, via A. da Giussano 10, 21052, Busto Arsizio, VA, Italy.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't