Dept. Physiology and Pharmacology, University of Western Ontario, London, Ontario N6A 5C1, Canada.
Dept. Physiology and Pharmacology, University of Western Ontario, London, Ontario N6A 5C1, Canada.
Epilepsy Behav. 2019 Jul;96:1-5. doi: 10.1016/j.yebeh.2019.03.021. Epub 2019 May 8.
The objective of this project was to test whether a drug-induced model of temporal lobe seizures, namely seizures induced by a gamma aminobutyric acid (GABA) receptor antagonist, CGP35348, result in long-term disruption of hippocampal memory function. Seizures were induced in experimental rats by intracerebroventricular (i.c.v.) injection of CGP35348 (0.64 μmol in 3 μL) for three consecutive days; control rats received no injection. Rats were first trained to criterion on an open radial arm maze (RAM) with 4 of the 8 arms baited, then received seizure and control treatment, and tested again on the RAM during the first week (days 1-5) and fourth week (days 22-29) after the last injection. An initial i.c.v. CGP35348 injection induced a mean of 4.4 seizures in the hippocampus, often accompanied with stages 3-5 convulsions, and sometimes with jumping; three daily CGP35348 injections induced 10.4 ± 1.8 (n = 7 rats) seizures in total. In two separate experiments, seizure-treated rats performed worse than control rats in working memory (WM) during both the 1st and 4th weeks after seizures. Reference memory (RM) deficit during the 1st week after seizures was observed in only one experiment in which RM was acquired >2 weeks ago. The memory deficits were not accompanied by gross neuronal loss in the hippocampus. In conclusion, i.c.v. injection of a GABA receptor antagonist in adult rats induced brief, multiple, focal hippocampal seizures that induced deficits in spatial memory for up to 4 weeks.
本项目的目的是检验一种颞叶癫痫的药物诱导模型，即γ-氨基丁酸（GABA）受体拮抗剂 CGP35348 诱导的癫痫，是否会导致海马记忆功能的长期障碍。实验大鼠通过侧脑室（i.c.v.）连续 3 天注射 CGP35348（3μL 中 0.64μmol）来诱发癫痫；对照组大鼠未接受注射。大鼠首先在开放的放射臂迷宫（RAM）上接受 4 个臂位诱饵的训练，然后接受癫痫和对照治疗，并在最后一次注射后的第 1 周（第 1-5 天）和第 4 周（第 22-29 天）再次在 RAM 上进行测试。初次 i.c.v. CGP35348 注射在海马中诱发了平均 4.4 次癫痫发作，通常伴有 3-5 级惊厥，有时伴有跳跃；3 次每日 CGP35348 注射总共诱发了 10.4±1.8 次癫痫发作（n=7 只大鼠）。在两项独立的实验中，癫痫发作后的第 1 周和第 4 周，癫痫发作治疗组的大鼠在工作记忆（WM）方面的表现均比对照组差。只有在一个实验中观察到，在 RM 是在 2 周以上之前获得的情况下，癫痫发作后第 1 周的参考记忆（RM）缺陷。记忆缺陷没有伴随着海马神经元的大量丢失。总之，成年大鼠侧脑室注射 GABA 受体拮抗剂可诱发短暂、多次、局灶性海马癫痫发作，导致空间记忆缺陷长达 4 周。
