DIAZEPAM EFFECTS ON RECOVERY OF FUNCTION

地西泮对功能恢复的影响

• 批准号: 3408122
• 负责人: TIMOTHY SCHALLERT
• 金额: $ 7.35万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-08-01 至 1988-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3408122
• 关键词: amphetamines; anticonvulsants; basal ganglia; behavior test; brain injury; centrally acting drug; convulsants; dexamethasone; diazepam; dosage; experimental brain lesion; longitudinal animal study; neuropharmacology; phenobarbital; phenytoin; sedative /hypnotic; sensory cortex; sensory disorders; somesthetic sensory cortex

This project explores the possibility that there is a critical period shortly following brain damage during which the mechanisms of recovery of function are highly vulnerable to disruption. As a model of brain damage, rats will receive unilateral antero-medial cortex lesions, which yield a precisely-quantified sensory asymmetry that reliably recovers within about 8 days. Some of the animals will be exposed postoperatively to daily injections of diazepam. In recent work we found that a diazepam regimen beginning at 12 hrs after surgery and continuing for 3 postoperative weeks completely disrupts recovery from the lesion-induced sensory asymmetry for an indefinite period. Sedation or ataxia could be ruled out because the efficiency and speed (as opposed to the symmetry) of behavior were not impaired. As long as 10 weeks after discontinuation of the drug (the duration of our observations), no recovery occurred. We also found that if the initial injection of diazepam is administered after recovery occurs, only a very transient (or no) asymmetry appears, even if the dose of chronic diazepam is raised. We plan to confirm these observations, to extend the duration of testing to 12 months or more after the discontinuation of the drug regimen, and to determine whether other lesions and other symptoms of brain damage are affected in the same way. It seems especially noteworthy that there may be a critical stage of events after brain damage in which the recovery process is vulnerable to profound, perhaps permanent, disruption. The onset and length of this critical period, the minimum effective dose of diazepam, the effects of co-administration of benzodiazepine antagonists, and the effects of other agents on recovery (including GABA agonists or other drugs with anti-convulsant properties commonly used clinically to treat or prevent seizures following brain damage) are among the questions we plan to address.

该项目探讨了存在关键时期的可能性 脑损伤后不久，恢复机制 功能极易受到干扰。 作为脑损伤的模型， 大鼠将接受单侧前内侧皮质损伤，从而产生 精确量化的感觉不对称可在大约 8天。 有些动物术后每天都会暴露在 注射地西泮。 在最近的工作中，我们发现地西泮疗法 从手术后 12 小时开始，持续术后 3 周 完全破坏了损伤引起的感觉不对称的恢复 无限期。 可以排除镇静或共济失调，因为 行为的效率和速度（相对于对称性）并没有 受损。 停药后长达 10 周（ 我们观察的持续时间），没有发生恢复。 我们还发现，如果 恢复后首次注射地西泮， 即使剂量 慢性地西泮升高。 我们计划确认这些观察结果 将测试持续时间延长至 12 个月或更长时间 停止药物治疗，并确定是否有其他病变 脑损伤的其他症状也会以同样的方式受到影响。 它似乎 尤其值得注意的是，事态发展之后可能会出现一个关键阶段。 脑损伤的恢复过程很容易受到严重的、 也许是永久性的、破坏性的。 这个临界点的开始和持续时间 期间，地西泮的最小有效剂量，效果 苯二氮卓类拮抗剂的共同给药以及其他药物的影响 恢复药物（包括 GABA 激动剂或其他具有疗效的药物） 临床上常用于治疗或预防的抗惊厥特性 脑损伤后的癫痫发作）是我们计划解决的问题之一。