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


CONCLUSIONS
Agmatine prevented tolerance to and substance dependence on morphine in mice by activation of imidazoline receptors.
Li
J
J
Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, China.
Li
X
X
Pei
G
G
Qin
B Y
BY
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000376:Agmatine / Q000494:pharmacology / Q000627:therapeutic use*; D000701:Analgesics, Opioid / Q000009:adverse effects*; D000818:Animals; D004361:Drug Tolerance; D005260:Female; D019329:Idazoxan / Q000494:pharmacology; D008297:Male; D051379:Mice; D009020:Morphine / Q000009:adverse effects*; D009021:Morphine Dependence / Q000517:prevention & control*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*
D000317:Adrenergic alpha-Antagonists; D000701:Analgesics, Opioid; D000376:Agmatine; D009020:Morphine; D019329:Idazoxan