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Clonidine potentiation of morphine discriminative stimulus‐modulated by alpha2 noradrenergic receptor mechanism
Author(s) -
Li SuMin,
Katz Jonathan L.
Publication year - 2006
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.20.4.a680-d
Subject(s) - idazoxan , clonidine , morphine , yohimbine , atipamezole , opioid , antagonist , locus coeruleus , pharmacology , long term potentiation , anesthesia , psychology , medicine , prazosin , medetomidine , receptor , central nervous system , heart rate , blood pressure
Previous studies demonstrated that alpha2 agonists can be used to potentiate opioid analgesia and reduce the opioid withdrawal syndrome. The purpose of the present experiment was to further document interactions of the alpha2 noradrenergic and opioid systems with regard to the subjective effects of morphine using rats trained to discriminate 3 mg/kg morphine from saline under a fixed‐ratio schedule of food presentation. Once subjects were trained, a range of doses of morphine produced dose‐dependent increases in morphine‐appropriate responding. This effect was potentiated by clonidine, lofexidine and medetomidine, while there was no significant change produced by the alpha2 antagonists: yohimbine, idazoxan and atipamezole. Partial substitution for morphine produced by clonidine was blocked by idazoxan and atipamezole. The potentiation of morphine discriminative stimulus by clonidine was also blocked by idazoxan and atipamezole. Though clonidine only partially substituted for morphine, an effect often characterized as non‐specific, those effects were dose‐dependently blocked by alpha2 antagonists, as was the potentiation of the subjective effects of morphine. These results suggest that, as with analgesia and dependence, there is a specific involvement of the noradrenergic system in the subjective effects of morphine in rats.