| 英文摘要 |
Objective: Subanesthetic doses of ketamine could induce transient psychotic features such as hallucinations and delusions, mimicking the core symptoms of schizophrenia. In this study, we intended to investigate the pharmacological effects of risperidone and valproic acid (VPA) on ketamine-induced locomotor activity. Methods: Behavioral assessments, including open-field testing with video-tracking system and gait analysis, were conducted on male C57BL/6J mice treated with study drugs or ketamine. After a 30-min habituation period, mice were intraperitoneally (i.p.) injected with either risperidone (0 or 0.1 mg/kg) or VPA (0 or 200 mg/kg). Locomotor activity was recorded for 30 min following this injection. Ketamine (0 or 25 mg/kg) was then administered intraperitoneally, and locomotor activity was recorded for an additional 30 min. Travelled distance and duration spent in the central area were measured following drug treatments. Results: Neither risperidone nor VPA alone had a significant effect on the locomotor activity. However, ketamine administration significantly increased both the total distance traveled and the duration spent in the center of the open field. Risperidone at 0.1 mg/kg completely inhibited ketamine-induced hyperlocomotion compared to the vehicle group (p < 0.001), while VPA at 200 mg/kg partially suppressed the effect. Neither risperidone nor VPA significantly reversed the ketamine-induced increase in the duration spent in the central area. Conclusion: This study demonstrates that risperidone and VPA modulate ketamine-induced hyperlocomotion in mice. Risperidone provided complete suppression, while VPA partially suppressed hyperlocomotion, suggesting its potential as an adjunct therapy for schizophrenia through the modulation of glutamatergic pathways. |
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