De Sarro G, Palma E, Costa N, Marra R, Gratteri S, De Sarro A, Rotiroti D
Department of Experimental and Clinical Medicine, Faculty of Medicine and Surgery, University of Catanzaro Magna Grecia, Policlinico Mater Domini, Via T. Campanella, 88100 Catanzaro, Italy.
Neuropharmacology. 2000 Aug 23;39(11):2147-61. doi: 10.1016/s0028-3908(00)00050-2.
The involvement of GABA(B) receptors in the behavioural and epileptic electrocortical discharges occurring in chemical kindling induced by repeated treatments with a subconvulsant dose of pentylenetetrazole (25 mg/kg i.p.) has been investigated in CD1 mice. Behavioural and electrocorticographic epileptic seizures following kindling induced by pentylenetetrazole (25 mg/kg i.p.) were attenuated or completely antagonized in a dose-dependent manner by the GABA(B) receptor agonist R-baclofen (2 and 6 mg/kg) whilst the GABA(B) receptor antagonist 3-amino-propyl-diethoxy-methyl-phosphinic acid (CGP 35348, 25, 50 or 100 mg/kg) and 3-[1-(S)-(3, 4-dichloro-phenyl-ethyl]amino-2-(S)-hydroxy-propyl-benzyl-phosphinic acid (CGP 55845A, 10 or 20 mg/kg) produced a more rapid development of kindling and an increase in behavioural and electrocorticographic epileptic changes. In addition, all GABA(B) receptor antagonists were able to induce an increase in Fos and Jun protein expression in pentylenetetrazole (25 mg/kg i.p.) treated mice whilst the GABA(B) receptor agonist R-baclofen (2 or 6 mg/kg) attenuated the expression of Fos and Jun protein, at cortical and limbic structures. In order to study the persistence of changes induced by pentylenetetrazole kindling, different groups of mice were rechallenged with a kindling stimulus 15 or 30 days after withdrawal from the last injection of vehicle+pentylenetetrazole, R-baclofen+pentylenetetrazole or GABA(B) receptor antagonists+pentylenetetrazole. The groups receiving GABA(B) receptor antagonists+pentylenetetrazole showed a higher incidence of seizures following the kindling stimulus than mice receiving vehicle+pentylenetetrazole whilst animals treated with R-baclofen were protected from the kindling stimulus. The different effects observed following repeated treatment with the GABA(B) receptor agonist and antagonist used revealed that GABA(B) receptors are able to affect the development of the epileptic kindling state induced by pentylenetetrazole.
在CD1小鼠中，研究了γ-氨基丁酸B（GABA(B) )受体在由亚惊厥剂量的戊四氮（25毫克/千克腹腔注射）重复处理诱导的化学点燃过程中所出现的行为和癫痫性皮质电活动中的作用。戊四氮（25毫克/千克腹腔注射）诱导点燃后的行为和皮质脑电图癫痫发作，被GABA(B)受体激动剂R-巴氯芬（2和6毫克/千克）以剂量依赖性方式减弱或完全拮抗，而GABA(B)受体拮抗剂3-氨基丙基-二乙氧基-甲基-次膦酸（CGP 35348，25、50或100毫克/千克）和3-[1-(S)-(3,4-二氯苯基-乙基]氨基-2-(S)-羟基丙基-苄基-次膦酸（CGP 55845A，10或20毫克/千克）使点燃发展更快，行为和皮质脑电图癫痫变化增加。此外，所有GABA(B)受体拮抗剂都能使戊四氮（25毫克/千克腹腔注射）处理的小鼠中Fos和Jun蛋白表达增加，而GABA(B)受体激动剂R-巴氯芬（2或6毫克/千克）在皮质和边缘结构处减弱Fos和Jun蛋白的表达。为了研究戊四氮点燃诱导的变化的持续性，在末次注射赋形剂+戊四氮、R-巴氯芬+戊四氮或GABA(B)受体拮抗剂+戊四氮后15或30天，用点燃刺激对不同组的小鼠进行再次激发。接受GABA(B)受体拮抗剂+戊四氮的组在点燃刺激后癫痫发作的发生率高于接受赋形剂+戊四氮的小鼠，而用R-巴氯芬处理的动物受到点燃刺激的保护。使用GABA(B)受体激动剂和拮抗剂重复处理后观察到的不同效应表明，GABA(B)受体能够影响戊四氮诱导的癫痫点燃状态的发展。
