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Comparison of antagonist potency to evoke an acute withdrawal stimulus 4 h after pretreatment with morphine in rats
Author(s) -
Hazel Kweku Dodoo,
Fluck Jonathan,
Jones Nicholas T.,
Evola Marianne,
Young Alice M.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.712.2
Subject(s) - morphine , potency , naltrexone , nalbuphine , opioid antagonist , agonist , stimulus (psychology) , opioid , stimulus control , antagonist , pharmacology , saline , medicine , narcotic antagonist , endocrinology , anesthesia , (+) naloxone , chemistry , psychology , receptor , in vitro , biochemistry , nicotine , psychotherapist
In vivo behavioral experiments evaluated potency of opioid antagonists to evoke discriminative stimulus effects associated with acute morphine withdrawal. Rats were trained, on a food‐reinforced task, to discriminate naltrexone (Ntx; 0.32 mg/kg) 4 h after pretreatment with either 5.6 mg/kg morphine (MS) or saline. Dose‐effect tests assessed the ability of other opioid antagonists to mimic the MS/Ntx stimulus; all injections were given by subcutaneous injection. Ntx itself (0.001 – 1.0 mg/kg) and naloxone (0.001 – 0.32 mg/kg) both dose‐dependently mimicked the MS/Ntx stimulus at doses that did not suppress response rates. Surprisingly, naloxone produced full MS/Ntx stimulus effects at lower doses than did Ntx. In contrast, 6‐β naltrexol (0.32 – 10 mg/kg) evoked a maximum of 60% generalization to the MS/Ntx stimulus and did not suppress response rates markedly. The partial agonist nalbuphine (0.32 – 32 mg/kg) produced full MS/Ntx stimulus effects at a dose of 32 mg/kg but suppressed responding markedly. These data suggest that opioid antagonists differ in potency to evoke acute withdrawal and may differ in their ability to evoke an acute maximal withdrawal stimulus effect. [Supported by NIH DA03796, GM 08167, and the Howard Hughes Medical Institute.]