Aim: To study the effects of agmatine on tolerance to and dependence on morphine.
Methods: Inhibitory effects of agmatine on tolerance to and substance dependence on morphine were observed in mouse tolerant models and in mouse jumping test, respectively.
Results: Agmatine 0.125-2.5 mg.kg-1 prevented the development of tolerant to morphine in a dose-dependent manner. Pretreatment of mice with morphine induced an over 3-fold increase in analgesic ED50 (20.1, 14.4-28.0 mg.kg-1) than those with normal saline (6.3, 5.1-7.8 mg.kg-1). Pretreatment of mice with both of agmatine and morphine made morphine loss the ability to induce tolerance. Withdrawal jumps and loss in body weight induced by naloxone in morphine-dependent mice were prevented by agmatine (2.5-10 mg.kg-1) in a dose-dependent manner. ED50 of naloxone (21.4, 18.4-24 mg.kg-1) required to precipitate withdrawal jumps in mice pretreated with both agmatine and morphine was 8 times higher than that with morphine alone (2.5, 2.1-2.8 mg.kg-1). These effects of agmatine were blocked by idazoxan.
Conclusion: Agmatine prevented tolerance to and substance dependence on morphine in mice by activation of imidazoline receptors.