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.