Crabbe J, Young E R, Dorow J
Research Service, Department of Veterans Affairs Medical Center, Portland, OR 97201.
Pharmacol Biochem Behav. 1994 Mar;47(3):443-50. doi: 10.1016/0091-3057(94)90141-4.
Mice selectively bred to be Withdrawal Seizure-Prone (WSP) or Seizure-Resistant (WSR) after chronic ethanol administration have been reported to be differentially sensitive to the anticonvulsant and proconvulsant effects on alcohol withdrawal of drugs interacting with glutamate receptors. Several behavioral effects of the noncompetitive glutamate receptor antagonist, dizocilpine, were determined in WSP and WSR mice to see whether their differential sensitivity generalized to effects unrelated to seizures, and to see whether it was only apparent during ethanol withdrawal. Dizocilpine potentiated the loss of righting reflex induced by ethanol, and dose-dependently stimulated habituated and nonhabituated open field activity. WSP and WSR mice were equally sensitive to these effects of dizocilpine. Pretreatment with dizocilpine increased the transcorneal amperage necessary to produce maximal electroshock seizures: WSR mice were more sensitive than WSP to this effect. Ethanol withdrawal (i.e., testing 6 h after a 24-h exposure to ethanol vapor) and dizocilpine had several effects on mice tested in the hole-in-wall apparatus. Several differences between WSP and WSR mice were also found, but in no case did dizocilpine differentially affect ethanol-withdrawing WSP and WSR mice. Across these experiments, differences between WSP and WSR mice in response to dizocilpine were rather specific. For some responses, WSP and WSR mice were equally sensitive, but only in the seizure-related measure assessed were naive WSR mice more sensitive than WSP.(ABSTRACT TRUNCATED AT 250 WORDS)
据报道，经过长期乙醇给药后，选择性培育出易发生戒断性癫痫（WSP）或抗癫痫（WSR）的小鼠，对与谷氨酸受体相互作用的药物在酒精戒断方面的抗惊厥和促惊厥作用具有不同的敏感性。在WSP和WSR小鼠中测定了非竞争性谷氨酸受体拮抗剂地卓西平的几种行为效应，以观察它们的不同敏感性是否扩展到与癫痫无关的效应，以及这种差异是否仅在乙醇戒断期间才明显。地卓西平增强了乙醇诱导的翻正反射丧失，并剂量依赖性地刺激了习惯化和非习惯化的旷场活动。WSP和WSR小鼠对地卓西平的这些效应同样敏感。用地卓西平预处理可增加产生最大电休克惊厥所需的经角膜电流：WSR小鼠比WSP小鼠对此效应更敏感。乙醇戒断（即，在暴露于乙醇蒸气24小时后6小时进行测试）和地卓西平对在洞壁装置中测试的小鼠有多种影响。还发现了WSP和WSR小鼠之间的一些差异，但地卓西平在任何情况下都没有对戒断乙醇的WSP和WSR小鼠产生不同的影响。在这些实验中，WSP和WSR小鼠对地卓西平反应的差异相当具体。对于某些反应，WSP和WSR小鼠同样敏感，但只有在评估的与癫痫相关的指标中，未接触过药物的WSR小鼠比WSP小鼠更敏感。（摘要截断于250字）
