Document Detail

Direct evidence for the involvement of the mesolimbic kappa-opioid system in the morphine-induced rewarding effect under an inflammatory pain-like state.
MedLine Citation:
PMID:  15257306     Owner:  NLM     Status:  MEDLINE    
Recent clinical studies have demonstrated that when morphine is used to control pain in cancer patients, psychological dependence is not a major concern. The present study was undertaken to ascertain the modulation of psychological dependence on morphine under a chronic pain-like state in rats. The prototypical mu-opioid receptor agonist morphine (8 mg/kg, i.p.) induced a dose-dependent place preference. In the present study, we found that an inflammatory pain-like state following formalin injection significantly suppressed the morphine-induced rewarding effect. This effect was almost reversed by s.c. pretreatment with the kappa-opioid receptor antagonist nor-binaltorphimine (nor-BNI, 5 mg/kg). Furthermore, the morphine-induced increase in dopamine (DA) turnover in the limbic forebrain was significantly inhibited by treatment with formalin. This inhibition was also suppressed by pretreatment with nor-BNI. In addition, in vivo microdialysis studies clearly showed that the morphine-induced increase in the extracellular levels of DA and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, in the nucleus accumbens (N.Acc.) was significantly decreased in rats that had been pretreated with formalin. This effect was in turn reversed by the microinjection of a specific dynorphin A antibody into the N.Acc. These findings suggest that the inflammatory pain-like state induced by formalin injection may have caused a sustained activation of the kappa-opioidergic system within the N.Acc., resulting in suppression of the morphine-induced rewarding effect in rats. The present study provides further evidence of the clinical usefulness of morphine in patients suffering from severe pain.
Minoru Narita; Yayoi Kishimoto; Yuya Ise; Yoshinori Yajima; Kaoru Misawa; Tsutomu Suzuki
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology     Volume:  30     ISSN:  0893-133X     ISO Abbreviation:  Neuropsychopharmacology     Publication Date:  2005 Jan 
Date Detail:
Created Date:  2004-12-20     Completed Date:  2005-01-26     Revised Date:  2014-03-25    
Medline Journal Info:
Nlm Unique ID:  8904907     Medline TA:  Neuropsychopharmacology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  111-8     Citation Subset:  IM    
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MeSH Terms
Brain Chemistry / drug effects
Conditioning, Operant / drug effects
Dopamine / metabolism
Dynorphins / pharmacology
Edema / chemically induced,  pathology
Foot / pathology
Formaldehyde / diagnostic use
Inflammation / chemically induced,  physiopathology*
Limbic System / drug effects,  metabolism,  physiology*
Morphine / pharmacology*
Naltrexone / analogs & derivatives*,  pharmacology
Narcotic Antagonists / pharmacology
Narcotics / pharmacology*
Pain / chemically induced,  physiopathology*
Pain Measurement / drug effects
Rats, Sprague-Dawley
Receptors, Opioid, kappa / physiology*
Reg. No./Substance:
0/Narcotic Antagonists; 0/Narcotics; 0/Receptors, Opioid, kappa; 105618-26-6/norbinaltorphimine; 1HG84L3525/Formaldehyde; 5S6W795CQM/Naltrexone; 74913-18-1/Dynorphins; 76I7G6D29C/Morphine; VTD58H1Z2X/Dopamine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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