Effect of MS-153 on the development of behavioral sensitization to locomotion- and ataxia-inducing effects of phencyclidine

Rationale: Repeated administration of phencyclidine (PCP) produces behavioral sensitization to PCP. Although the precise mechanism is unknown, glutamatergic neurotransmission seems to play an important role in the development of sensitization. Objectives: The present study examined whether a novel compound, MS-153 ((R)-(-)-5-methyl-1-nicotinyl-2-pyrazoline), which has an ability to enhance glutamate uptake and inhibit glutamate release, would block the development of behavioral sensitization to PCP. Methods: For studying effects of MS-153, locomotor activity was measured by an infrared sensor and ataxia was measured by a rating scale. Results: MS-153 (10 and 100 mg/kg) enhanced locomotion and ataxia induced by a single injection of PCP (7.5 mg/kg). Repeated administration of PCP (20 mg/kg, once in every day, for 5 days) developed sensitization to locomotion- and ataxia-inducing effects of PCP (7.5 mg/kg). MS-153 given 60 min and 120 min later of every PCP treatment blocked the development of behavioral sensitization to both locomotion- and ataxia-inducing effects of PCP. Co-administration of MS-153 with repeated saline treatment did not produce hypersensitivity to PCP. Conclusions: These results suggest that the attenuation of glutamatergic neural transmission enhances acute effects of PCP, in contrast, blocks the behavioral sensitization developed by repeated PCP treatment. Therefore, glutamatergic neural transmission plays an important role in the development of behavioral sensitization to PCP.