This study investigated the antidepressant-like effects of a chronic treatment with either tramadol (20 mg/kg, i.p.) or desipramine (10 mg/kg, i.p.) in the unpredictable chronic mild stress model of depression in BALB/c mice. Mice were first submitted to a 2 week drug-free unpredictable chronic mild stress before the onset of the treatments. The unpredictable chronic mild stress regimen induced a degradation of the state of the coat and decreased the grooming behaviour in the splash test. These physical and behavioural abnormalities were counteracted by tramadol and desipramine. Furthermore, we observed neither a significant acceleration nor diminution by pindolol (5-HT1A/1B receptor antagonist, 10 mg/kg, i.p.) on the antidepressant-like actions of desipramine and tramadol whereas yohimbine (alpha 2-adrenergic receptor antagonist, 2 mg/kg, i.p.) antagonized the antidepressant-like effects of both drugs during the unpredictable chronic mild stress regimen.