Linked Life Data

12604679

Source:http://linkedlifedata.com/resource/pubmed/id/12604679

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2003-2-26
pubmed:abstractText
Rats were trained to discriminate 4-h pretreatment with 10 mg/kg morphine and 15-min pretreatment with 0.3 mg/kg naltrexone (morphine-->naltrexone) from pretreatment with saline and 0.3 mg/kg naltrexone (saline-->naltrexone). The discrimination seems to derive from interoceptive stimuli from antagonist-precipitated withdrawal from acute morphine dependence. The purpose of this study was to extend pharmacological characterization of the discrimination by testing opioid agonists other than morphine and antagonists other than naltrexone. Of seven mu-opioid agonists tested in place of morphine, only two (heroin and levorphanol) substituted completely for it; trials completed on the morphine-->naltrexone-appropriate lever increased as a function of agonist and naltrexone dose. Agonists with intrinsic efficacy higher (etorphine, fentanyl, and methadone) or lower (buprenorphine and meperidine) than that of morphine substituted only partially. However, when naltrexone was administered during continuous infusion of fentanyl or methadone via s.c. osmotic pump, rats responded as if they had received morphine-->naltrexone; discriminative responding correlated with global withdrawal scores. Rats responded primarily on the saline-->naltrexone-appropriate lever when naltrexone was administered after pretreatment with dextrorphan, the dextrorotatory isomer of levorphanol, or kappa-opioid agonists (5-alpha,7-alpha,8-beta)-(+)-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro(4,5)dec-8-yl]-benzeneacetamide (U69,593) and spiradoline. Antagonists with no intrinsic efficacy at mu-opioid receptors (naloxone and diprenorphine) substituted completely for naltrexone, whereas those with some efficacy (nalorphine and levallorphan) substituted partially. Thus, morphine-->naltrexone-like stimulus control of behavior by drugs administered acutely requires pretreatment with certain mu-opioid agonists and a pure antagonist, is independent of agonist efficacy, and is stereoselective. Interoceptive stimuli from naltrexone-precipitated opioid withdrawal are more similar across morphine-like agonists during chronic dependence than they are during acute dependence.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
304
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1033-41
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Discrimination of a single dose of morphine followed by naltrexone: substitution of other agonists for morphine and other antagonists for naltrexone in a rat model of acute dependence.
pubmed:affiliation
Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322, USA. sholtzm@emory.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.