Becker Howard C, Myrick Hugh, Veatch Lynn M
Charleston Alcohol Research Center, Center for Drug and Alcohol Programs, Institute of Psychiatry, 67 President Street, Charleston, SC 29425, USA.
Alcohol Alcohol. 2006 Jul-Aug;41(4):399-406. doi: 10.1093/alcalc/agl029. Epub 2006 Apr 24.
Pregabalin has been shown to possess anticonvulsant, analgesic, and anxiolytic properties in a variety of testing situations. This study was designed to evaluate the ability of pregabalin to exert its anticonvulsant effects against behavioral and electrographic measures of CNS hyperexcitability associated with alcohol withdrawal in a mouse model of ethanol dependence.
Adult mice were chronically exposed to ethanol and, upon withdrawal, were tested for behavioral signs of seizure activity (handling-induced convulsions) or abnormalities in spontaneous EEG activity recorded from cortical and subcortical sites.
Pregabalin (50-200 mg/kg) administered 1 and 4 h into withdrawal dose dependently reduced severity of handling-induced convulsions in comparison to vehicle-treated mice. Similarly, pregabalin reduced the frequency in which EEG activity was interrupted by trains of high-voltage synchronous activity in a dose-related fashion. Finally, pregabalin treatment of repeated withdrawals was effective in blocking the development of withdrawal sensitization observed in vehicle-treated mice.
Collectively, these results suggest that pregabalin may be an effective therapeutic agent for medical management of alcohol detoxification.
在多种测试情况下,加巴喷丁已被证明具有抗惊厥、镇痛和抗焦虑特性。本研究旨在评估加巴喷丁在乙醇依赖小鼠模型中,针对与酒精戒断相关的中枢神经系统过度兴奋的行为和脑电图指标发挥抗惊厥作用的能力。
成年小鼠长期暴露于乙醇中,戒断时检测其癫痫活动的行为体征(处理诱导惊厥)或从皮质和皮质下部位记录的自发脑电图活动异常。
与给予赋形剂处理的小鼠相比,在戒断后1小时和4小时给予加巴喷丁(50 - 200毫克/千克)剂量依赖性地降低了处理诱导惊厥的严重程度。同样,加巴喷丁以剂量相关方式降低了脑电图活动被高压同步活动串中断的频率。最后,加巴喷丁对反复戒断的治疗有效阻断了在给予赋形剂处理的小鼠中观察到的戒断敏化的发展。
总体而言,这些结果表明加巴喷丁可能是酒精解毒医学管理的有效治疗药物。