File S E, Mabbutt P S, Becker A, Gonzalez L E, Fluck E
Psychopharmacology Research Unit, UMDS Division of Pharmacology, Guy's Hospital, London, United Kingdom.
Anxiety. 1996;2(3):109-16. doi: 10.1002/(SICI)1522-7154(1996)2:3<109::AID-ANXI1>3.0.CO;2-K.
Although there were no differences in response to an acute injection of pentylenetetrazole (PTZ), there were strain differences in the development of kindled seizures to repeated injections (PTZ; 30 mg/kg 3 times weekly for 13 injections), with Wistar rats reaching stage 4 or 5 of clonic-tonic seizures, but hooded Lister rats reaching only stage 2 or 3 of convulsive waves axially through the body. The strains also reacted differently to a test dose of PTZ (20 mg/kg) one week after the end of kindling, with the Wistar strain showing stage 3 and the Lister strain stage 2 seizures. When the rats were tested 24 h after the end of the kindling injections there was an anxiolytic effect in the social interaction test, in both the low light, familiar and the low light, unfamiliar test conditions that reached significance in the Wistar strain. The Wistar kindled rats showed an anxiolytic effect in the elevated plus-maze test of anxiety when they were tested 24 h after the end of kindling. The anxiolytic effects found 24 h after kindling could not be due to the seizure 24 h earlier, since no changes were found in rats tested 24 h after a single seizure from PTZ (60 mg/kg). When the rats were tested 1 week after the end of kindling there were no changes, compared with vehicle-injected controls, in either test of anxiety. There was no change in benzodiazepine binding in platelets of the kindled Lister rats but there was a significant increase in the kindled Wistar rats 1 week after the end of kindling and also 24 h after a single PTZ seizure. The pattern of increased platelet benzodiazepine binding did not correspond with the time course of rebound anxiolytic effects. However, after kindling it seems that there are long-lasting changes in benzodiazepine binding that are similar to the short-term increases that are found following a single seizure.
虽然对戊四氮(PTZ)进行急性注射时没有反应差异,但在对重复注射(PTZ;30mg/kg,每周3次,共注射13次)引发癫痫发作的发展过程中存在品系差异,Wistar大鼠达到阵挛 - 强直发作的4期或5期,而带帽利斯特大鼠仅达到全身轴向惊厥波的2期或3期。在点燃结束1周后,这两个品系对PTZ测试剂量(20mg/kg)的反应也不同,Wistar品系表现为3期发作,利斯特品系表现为2期发作。当在点燃注射结束后24小时对大鼠进行测试时,在社交互动测试中观察到抗焦虑作用,在低光照、熟悉和低光照、不熟悉的测试条件下,Wistar品系均达到显著水平。在点燃结束后24小时对Wistar点燃大鼠进行高架十字迷宫焦虑测试时,它们表现出抗焦虑作用。点燃后24小时发现的抗焦虑作用不可能是由于24小时前的癫痫发作,因为对单次PTZ(60mg/kg)癫痫发作后24小时测试的大鼠未发现变化。当在点燃结束后1周对大鼠进行测试时,与注射赋形剂的对照组相比,在任何焦虑测试中均未发现变化。点燃的利斯特大鼠血小板中的苯二氮䓬结合没有变化,但在点燃结束1周后以及单次PTZ癫痫发作后24小时,点燃的Wistar大鼠血小板中的苯二氮䓬结合有显著增加。血小板苯二氮䓬结合增加的模式与抗焦虑作用的反弹时间进程不对应。然而,点燃后似乎苯二氮䓬结合存在长期变化,类似于单次癫痫发作后发现的短期增加。