Dunworth S J, Stephens D N
Laboratory of Experimental Psychology, University of Sussex, Falmer, Brighton, UK.
Psychopharmacology (Berl). 1998 Apr;136(3):308-10. doi: 10.1007/s002130050571.
Mice were treated either with diazepam (15 mg/kg s.c. in oil), for 21 days, or for 3x7-day periods interspersed with two 72-h drug-free periods. Convulsant thresholds to pentylentetrazole infused into the tail vein 72 h following the final chronic treatment were lower in multiple-withdrawal mice than in mice which had experienced the same drug load, but only a single withdrawal, consistent with sensitisation of withdrawal events following previous withdrawal experience. The increase in seizure sensitivity of repeatedly withdrawn mice was prevented by treatment with the NMDA receptor antagonist CGP 39551 (20 mg/kg, i.p.) given once daily during the 3-day breaks in diazepam treatment, suggesting a role of glutamatergic transmission in the sensitisation process.
小鼠接受地西泮（15毫克/千克，皮下注射于油中）治疗21天，或接受3个7天疗程治疗，期间穿插两个72小时无药期。在末次长期治疗72小时后，经尾静脉注入戊四氮，多次撤药小鼠的惊厥阈值低于经历相同药物剂量但仅单次撤药的小鼠，这与既往撤药经历后撤药事件的敏化作用一致。在苯二氮䓬治疗的3天间歇期，每天一次腹腔注射NMDA受体拮抗剂CGP 39551（20毫克/千克），可防止反复撤药小鼠癫痫敏感性增加，提示谷氨酸能传递在敏化过程中起作用。
