Influence of idazoxan on analgesia, tolerance, and physical dependence of morphine in mice and rats in vivo

AIM: To study the influence of idazoxan (Ida), an antagonist of imidazoline receptors (I - R), on analgesia, tolerance, and physical dependence of mor phine. METHODS: The effects of Ida on pain threshold and morphine analgesia were observed in mouse acetic acid writhing test and 55 degreesC hot plate test. The effect of Ida on morphine tolerance and physical dependence were observed in mouse tolerant model and in mice and rat models. RESULTS: Ida (3 - 9 mg/kg) significantly decreased the pain threshold by 120 % in acetic acid writhing test and by 39 % in 55 degreesC hot plate test of mice, resp ectively. It inhibited the analgesic effect of morphine in a dose-dependent manner. Ida promoted the development of tolerance to morphine in mice and induced the abstinence syndrome in morphine-dependent mice and rats similar to naloxone. CONCLUSION: I-R and its endogenous ligand agmatine might part icipate in the pain threshold and influence morphine analgesia as well as n egatively regulate tolerance to and physical dependence on morphine.