Behavioral assessment of neuroleptic (3) Schizophrenia negative symptoms-like model induced by PCP

Immobility induced by force swimming is well known as an animal model of depression. To develop an animal model for the negative symptoms of schizophrenia, in particular, the depressive symptoms, the effect of Phencyclidine (PCP) on immobility in the forced swimming test was investigated in mice since PCP produces negative symptoms-like behavioral changes in humans. Repeated treatment with (10 mg/kg/day, sc, once a day for 14 days) prolonged the immobility time in the forced swimming test 24 hr after the final infection compared with saline treatment: the effect was not obtained by single treatment with PCP (10 mg/kg), or by repeated treatment with methamphetamine (0.3, and 1 mg/kg/day, sc, sc once a day for 14 days). The enhancing effect of PCP on the immobility persisted for at least 21 days after the withdrawal of the drug. Desipramine (10 mg/kg, pol) attenuated the immobility induced by the from swimming in mice repeated treated with saline. The enhancing effect of PCP on the immobility was attenuated by isperidone (0.3 mg/kg), clozapine (3 and 10 mg/kg), and desipramine (20 and 50 mg/kg), whereas haloperidol (0.3 and 1 mg/kg) had no effect. These result suggest that the enhancement of immobility in the forced swimming test brought about by repeated PCP treatment could becaused as a model of the negative symptoms, particularly the depression, of schizophrenia.