Research into novel therapeutic strategies for schizophrenia with high efficacy and low side effects has been progressed in recent years. In the present study, anti-schizophrenia activities of 2-(dimethylamino)- and 2-(methylamino)- 7H-naphtho[1,2,3-de]quinolin-7-one derivatives (D1-D10) have been evaluated in ketamine-induced experimental schizophrenia model in mice. For this aim, experimental animals was submitted to ketamine intraperitoneal injection at 100 mg/kg/day. Then, D1-D10 were administrated intra-cerebroventricularly to mice and in next step, animals depressive-like behaviors have been examined by despair swimming test. The obtained results demonstrate that 7H-naphtho[1,2,3- de]quinolin-7-one derivatives, specifically D9, reduced depressive-like behaviors via the decrease of the immobility time and the increase of the swim and climb times. Overall, these results showed that these alkaloids have anti-schizophrenia efficacy and due to their low side effects, they can be used as a new strategy for the treatment of depressive symptoms of schizophrenia patients.