Effects of Cilostazol on Cognitive Deficits in Mice after Repeated Administration of Phencyclidine
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Objective : To examine the effects of cilostazol, a selective inhibitor of type III phosphodiesterase (PDE), on cognitive deficits in mice after repeated administration of the N-methyl-D-aspartate (NMDA) receptor antagonist phencyclidine (PCP). Methods：Saline (10 ml/kg/day) or PCP (10 mg/kg/day) were administered subcutaneously to mice for 10 days (once daily on days 1−5 and 8−12). Three days (day 15) after the final administration of saline or PCP, vehicle (0.5% carboxymethylcellulose)or cilostazol (0.3, 3, 10 or 30 mg/kg/day) were administered orally for 14 consecutive days (once daily on days 15−28). The novel object recognition test (NORT) was performed 24 hours (day 29) after the final administration. Results：In the NORT, PCP -induced cognitive deficits in mice were improved significantly by subsequent sub-chronic (14 days)administration of cilostazol (3, 10 or 30 mg/kg/day), but not by the lowest dose of cilostazol (0.3 mg/kg/day). Conclusion：This study suggests that cilostazol ameliorates PCP-induced cognitive deficits in mice. Therefore, it is likely that cilostazol has therapeutic potential for cognitive deficits in schizophrenia.
Abstract
Objective : To examine the effects of cilostazol, a selective inhibitor of type III phosphodiesterase (PDE), on cognitive deficits in mice after repeated administration of the N-methyl-D-aspartate (NMDA) receptor antagonist phencyclidine (PCP). Methods：Saline (10 ml/kg/day) or PCP (10 mg/kg/day) were administered subcutaneously to mice for 10 days (once daily on days 1−5 and 8−12). Three days (day 15) after the final administration of saline or PCP, vehicle (0.5% carboxymethylcellulose)or cilostazol (0.3, 3, 10 or 30 mg/kg/day) were administered orally for 14 consecutive days (once daily on days 15−28). The novel object recognition test (NORT) was performed 24 hours (day 29) after the final administration. Results：In the NORT, PCP -induced cognitive deficits in mice were improved significantly by subsequent sub-chronic (14 days)administration of cilostazol (3, 10 or 30 mg/kg/day), but not by the lowest dose of cilostazol (0.3 mg/kg/day). Conclusion：This study suggests that cilostazol ameliorates PCP-induced cognitive deficits in mice. Therefore, it is likely that cilostazol has therapeutic potential for cognitive deficits in schizophrenia.
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