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Zhongguo Yao Li Xue Bao. 1999 Mar;20(3):232-8.

Effects of agmatine on tolerance to and substance dependence on morphine in mice.

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1
Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, China.

Abstract

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.

PMID:
10452098
[Indexed for MEDLINE]
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