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Updated: Aug 24, 2026

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Involvement of histaminergic system in the discriminative stimulus effects of morphine
Tomohisa Mori1, Minoru Narita, Kenji Onodera
1Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
Abstract:
The interactions between morphine and the histaminergic system are not yet fully clarified. More especially, the involvement of the histaminergic system in the discriminative stimulus effects of morphine has not been determined. Therefore, the effects of histamine-related compounds on the discriminative stimulus effects of morphine were examined in rats. Combination tests using histamine-related compounds with morphine were initiated in rats trained to discriminate between 3.0 mg/kg morphine and saline. Zolantidine (central histamine H2-receptor antagonist), but not pyrilamine (central histamine H1-receptor antagonist) or ranitidine (peripheral histamine H2-receptor antagonist), significantly attenuated the discriminative stimulus effects of morphine. The histamine precursor L-histidine significantly potentiated the discriminative stimulus effects of morphine. These results suggest that the discriminative stimulus effects of morphine are, at least in part, mediated through the central activation of histamine H2-receptors in rats.
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