Effect of MS-153 on the development of behavioral sensitization to stereotypy-inducing effect of phencyclidine

The present study examined the effects of a novel compound, MS-153 [(R)-(-)-5-methyl-1-nicotinyl-2-pyrazoline], which has an ability to enhance glutamate uptake and inhibit glutamate release, on the development of behavioral sensitization to phencyclidine (PCP). MS-153 (10 and 100 mg/kg) enhanced stereotypy induced by a single injection of PCP (7.5 mg/kg). Repeated administration of PCP (20 mg/kg, once every day for 5 days) enhanced stereotypy-inducing effects of PCP (7.5 mg/kg) when tested 4 days after the withdrawal from the repeated PCP treatment, indicating the development of behavioral sensitization. MS-153 given 60 and 120 min after the PCP treatments blocked the development of behavioral sensitization to stereotypy-inducing effects of PCP. These results suggest that the attenuation of glutamatergic neural transmission enhances acute effect of PCP, but in contrast, blocks the behavioral sensitization to PCP.