This study is to explore a behavioral and pathological model for depression in mice, and evaluate the anti-depressant-like effect of agmatine.  Neonatal Kunming mice were treated with fluoxetine (10 mg·kg⁻¹, ip, qd) for 17 d (between day 4 and 21 after birth), and then the mice were normally housed till being adult (about 10 weeks after birth).  The behaviors of the mice were measured by using open-field test, novelty suppressed feeding test and tail-suspension test.  Hippocampal adenylate cyclase (AC) activity was measured by radioimmunoassay.  Neonatal exposure to fluoxetine induced a “depression-like” behaviors in the adult mice, shown as the decreased locomotor activity, increased feeding latency and immobility time in the open-field test, novelty suppressed feeding test, and tail-suspension test, respectively.  Chronic agmatine treatment (10 mg·kg⁻¹, ig, bid) for 3 weeks significantly increased the locomotor activity, and decreased the feeding latency in the neonatal fluoxetine exposed mice.  Furthermore, single treatment with agmatine (40 mg·kg⁻¹, ig) also decreased the   immobility time in the tail-suspension test, and increased the hippocampal AC activity in the mice.  These results indicate that neonatal exposure to fluoxetine induces depressive-like behaviors in the adult mice.  Agmatine  reverses these behaviors, which may be closely related to the enhancement of the hippocampal AC activity.