Agmatine derived from arginine is recently considered as a neurotransmitter and/or neuromodulator that potentiates mor phine analgesia and inhibits the symptoms of naloxone-precipitated withdrawal in morphine dependent rats.The exact mechanisms of the inhibition of agmatine are not completdy known.Recently,more and more results indicate that down-regulation of hippocam pal neurogenesis is involved in opioid physical dependence.Therefore, the present study was undertaken to investigate the re lationships between agmatine anti-abstinent syndrome and its inhi bition on down-regulation of hippocampal neurogenesis in mor phine dependent rats, and the possible mechanisms.We found that the chronic pretreatment with morphine induced a classical naloxone-precipitated abstinent syndrome and a decrease in neuro genesis by 23% in the adult rat hippocampal granule cell layer compared with those of saline control.Co-administration of agma tine with morphine was able to inhibit significantly the abstinent syndrome and the decrease in neurogenesis in the adult rat hipp ocampal granule cell layer at same time.Furthermore, agmatine inhibited the decreased hippocampal expression of brain-derived neurotrophic factor and phosphorylated CREB, in response to chronic pretrentment with morphine.On the other hand, pretreat ment with agmatine in vitro significantly increased the proliferation of cultured hippocampal progenitor cells.All these results suggest that ngmatine could inhibit morphine-induced physical dependence by up-regulation of the expression of brain-derived neurotrophic factor and cell proliferation in the adult rat hippocampus.Al though agnatine is thought to ameliorate morphine dependence in multiple ways, the neurotrophic pathway may be one of the most important routes.