AGMATINE INHIBITED TOLERANCE TO AND DEPENDENCE ON MORPHINE IN GUINEA-PIG ILEUM IN-VITRO

ATM: To observe effect of agmatine (Agm) on tolerance to and substance dependence on morphine (Mor) in guinea pig ileum longitudinal muscle (GPILM). METHODS: The experiment was performed in electric field stimu lation (EFS) test in vitro. RESULTS: Mor inhibited twitch contractions of GPILM induced by EFS [IC50 = 140 (107 - 182) nmol . L-1]. Incubati on of GPILM with Mor 270 nmol . L-1 for 8 h evoked a 37-fold increase in IC50 of Mor (tolerance) and a contractile response to naloxone (Nal , substance dependence). When the preparations were coincubated with M or + Nal and Mor + Agm, Mor lost the ability to induce tolerance and i nhibited the contractile responses of the preparations to Nal by 90% a nd 75%, respectively. These effects of Agm could be almost completely antagonized by idazoxan. CONCLUSION: Agm prevented the development of tolerance to and substance dependence on Mor in GILM in vitro by activ ation of imidazoline receptors.