EFFECTS OF ANTIDEPRESSANTS ON PHENCYCLIDINE-INDUCED ENHANCEMENT OF IMMOBILITY IN A FORCED SWIMMING TEST IN MICE

We have previously found that repeated phencyclidine (PCP) treatment e nhances the immobility induced by forced swimming and suggested that t his behavioral change could be used as a model of the negative symptom s, particularly depression, of schizophrenia. The present study attemp ted to examine the effects of antidepressants on the depressive states (immobility) induced by forced swimming in mice repeatedly treated wi th PCP, compared with those in mice repeatedly treated with saline. In mice repeatedly treated with saline, desipramine (5 and 10 mg/kg) and imipramine (5 and 10 mg/kg) significantly attenuated immobility, wher eas mianserin (5-20 mg/kg) and clomipramine (10 and 50 mg/kg) had no a ffect. In mice repeatedly treated with PCP, the enhancing effect of PC P on immobility was attenuated by mianserin (5-20 mg/kg) at doses whic h did not have any effect in saline-treated mice, and by desipramine a t higher doses (20 and 50 mg/kg). However, imipramine (5-20 mg/kg) and clomipramine(10-50 mg/kg) did not affect PCP-induced enhancement of i mmobility. In the biochemical study, the content of 5-hydroxyindoleace tic acid (5-HIAA) and the 5-HIAA/5-hydroxytryptamine (5-HT) ratio in t he prefrontal cortex in mice repeatedly treated with PCP, but not with saline, following the forced swimming test were significantly increas ed, compared with those in the corresponding control mice (which did n ot perform the test). The present findings suggest that the depressive states induced by the forced swimming in mice repeatedly treated with PCP are less sensitive to acute treatment with tricyclic antidepressa nts, and this may be due to increase in 5-HT turnover. Antidepressants such as mianserin, which have the 5-HT, receptor antagonist propertie s, may be useful for the treatment of negative symptoms of schizophren ia. (C) 1997 Elsevier Science B.V.