Source:http://linkedlifedata.com/resource/pubmed/id/16935424
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1-3
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| pubmed:dateCreated |
2006-11-22
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| pubmed:abstractText |
Studies implicate endocannabinoids in the acute and chronic actions of opioid drugs, including the genesis of physical dependence. Previous evidence suggests that spinal release of calcitonin gene-related peptide (CGRP) and activation of its receptors contribute to opioid physical dependence. The release of CGRP at the spinal level is modulated by cannabinoid (CB1)-receptors. Thus, this study examined whether CB1-receptor activity mediates changes in CGRP underlying development of opioid physical dependence. Systemic morphine administration for 5-days elevated CGRP-immunoreactivity in the rat spinal dorsal horn. In situ hybridization of dorsal root ganglion (DRG) neurons revealed an increase in CGRP mRNA during initial (day 1-3) but not later phase (day 4-5) of morphine treatment. CGRP-immunoreactivity in DRG neurons, however, was increased in the later phase of morphine treatment. Naloxone challenge to morphine-treated animals precipitated an intense withdrawal syndrome that depleted CGRP-immunoreactivity and increased Fos expression in the dorsal horn. The Fos-response primarily occurred in neurons that expressed CGRP receptor component protein (RCP) suggesting CGRP activity contributes to neuronal activation during precipitated withdrawal. Spinal slices obtained from morphine-treated animals showed higher levels of CGRP release than from saline controls. Intrathecal co-administration of CB1-receptor antagonists, AM-251 or SR141716A, with daily morphine attenuated the behavioral manifestations of withdrawal. Treatment with AM-251 also reduced the depletion of CGRP, suppressed Fos-induction, and prevented the increase in capsaicin-evoked spinal CGRP release. Altogether, this study suggests that endocannabinoid activity, expressed via CB1-receptors, contributes to the induction of opioid physical dependence through spinal modulation of CGRP.
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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/AM 251,
http://linkedlifedata.com/resource/pubmed/chemical/Calcitonin Gene-Related Peptide,
http://linkedlifedata.com/resource/pubmed/chemical/Cannabinoids,
http://linkedlifedata.com/resource/pubmed/chemical/Capsaicin,
http://linkedlifedata.com/resource/pubmed/chemical/Endocannabinoids,
http://linkedlifedata.com/resource/pubmed/chemical/Morphine,
http://linkedlifedata.com/resource/pubmed/chemical/Naloxone,
http://linkedlifedata.com/resource/pubmed/chemical/Narcotic Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Piperidines,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-fos,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrazoles,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Cannabinoid, CB1
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| pubmed:status |
MEDLINE
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| pubmed:month |
Dec
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| pubmed:issn |
1872-6623
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
15
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| pubmed:volume |
126
|
| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
256-71
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| pubmed:dateRevised |
2008-11-21
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| pubmed:meshHeading |
pubmed-meshheading:16935424-Animals,
pubmed-meshheading:16935424-Calcitonin Gene-Related Peptide,
pubmed-meshheading:16935424-Cannabinoids,
pubmed-meshheading:16935424-Capsaicin,
pubmed-meshheading:16935424-Drug Administration Schedule,
pubmed-meshheading:16935424-Endocannabinoids,
pubmed-meshheading:16935424-Ganglia, Spinal,
pubmed-meshheading:16935424-Hot Temperature,
pubmed-meshheading:16935424-Immunologic Techniques,
pubmed-meshheading:16935424-Male,
pubmed-meshheading:16935424-Morphine,
pubmed-meshheading:16935424-Naloxone,
pubmed-meshheading:16935424-Narcotic Antagonists,
pubmed-meshheading:16935424-Neurons,
pubmed-meshheading:16935424-Nociceptors,
pubmed-meshheading:16935424-Opioid-Related Disorders,
pubmed-meshheading:16935424-Piperidines,
pubmed-meshheading:16935424-Proto-Oncogene Proteins c-fos,
pubmed-meshheading:16935424-Pyrazoles,
pubmed-meshheading:16935424-RNA, Messenger,
pubmed-meshheading:16935424-Rats,
pubmed-meshheading:16935424-Rats, Sprague-Dawley,
pubmed-meshheading:16935424-Receptor, Cannabinoid, CB1,
pubmed-meshheading:16935424-Spinal Cord,
pubmed-meshheading:16935424-Substance Withdrawal Syndrome
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| pubmed:year |
2006
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| pubmed:articleTitle |
Spinal modulation of calcitonin gene-related peptide by endocannabinoids in the development of opioid physical dependence.
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| pubmed:affiliation |
Department of Pharmacology and Toxicology and Anesthesiology, Queen's University Kingston, Ont., Canada K7L 3N6.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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