Effects of intragastric agmatine on morphine-induced physiological dependence in beagle dogs and rhesus monkeys.
Our previous studies demonstrated that subcutaneous injection of agmatine inhibits tolerance to and physiological dependence on morphine in mice and rats. In the present study we further evaluated the effects of intragastric (i.g.) administration of agmatine on morphine-induced physiological dependence in mice, rats, beagle dogs and rhesus monkeys. When agmatine (5-40 mg/kg, i.g.) was co-administered with morphine during the development of morphine-induced physiological dependence, it inhibited the abstinent syndrome precipitated by naloxone in mice, rats and beagle dogs. In addition, agmatine (40 mg/kg, i.g.) inhibited the abstinent syndrome precipitated by naloxone in mice when it was administered on the test day. In naloxone precipitated and naturally abstinent morphine dependent model in rhesus monkeys, agmatine (40 or 80 mg/kg, i.g.) inhibited the development of physiological dependence when it was co-administered with morphine. After the development of morphine dependence, agmatine (80 mg/kg, i.g.) inhibited the naturally abstinent syndrome during the 7-d abstinent period. All these results suggested that intragastric administration of agmatine inhibits morphine-induced physiological dependence in animal models.
Su
Rui-Bin
RB
Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
Lu
Xin-Qiang
XQ
Huang
Yu
Y
Liu
Yin
Y
Gong
Zheng-Hua
ZH
Wei
Xiao-Li
XL
Wu
Ning
N
Li
Jin
J
D000376:Agmatine / Q000008:administration & dosage / Q000494:pharmacology*; D000701:Analgesics, Opioid; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D007441:Intubation, Gastrointestinal; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D009020:Morphine; D009021:Morphine Dependence / Q000517:prevention & control* / Q000523:psychology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome / Q000523:psychology
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D009270:Naloxone; D000376:Agmatine; D009020:Morphine