Xu S G, Garant D S, Sperber E F, Moshé S L
Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461.
Brain Res. 1991 Dec 6;566(1-2):108-14. doi: 10.1016/0006-8993(91)91687-v.
There is evidence implicating the nigral gamma-aminobutyric acid (GABA) system in the control of seizures. Our previous studies have demonstrated that, in rat pups, intranigrally infused gamma-vinyl-GABA (GVG, 5-20 micrograms) strongly suppresses flurothyl-induced tonic but not clonic seizures. Furthermore, nigral infusions of bicuculline or muscimol abolish the anticonvulsant effect of GVG. In this study, we report that in adult rats bilateral infusions of GVG (20 micrograms) into the substantia nigra pars reticulata (SNR) significantly elevated the thresholds for both clonic and tonic seizures induced by flurothyl. Lower doses (5 and 10 micrograms) did not significantly protect adult rats against seizures, but there was a significant effect of GVG dose. Unilateral infusion of GVG (20 micrograms) in the SNR did not alter the thresholds for flurothyl-induced seizures. Intranigral infusions of bicuculline following pretreatment with GVG abolished the protective effect of GVG on flurothyl-induced seizures, indicating that the anticonvulsant effect of GVG is most likely mediated by the nigral GABAA receptor. Intranigral administration of muscimol after GVG pretreatment significantly suppressed flurothyl-induced seizures, but the combined effect of the two drugs was not as strong as that of GVG alone. The data suggest that GVG protects adult rats against flurothyl-induced seizures. In adults, however, the dose of GVG required to protect against both clonic and tonic seizures is higher than that needed in rat pup SNR.
有证据表明黑质γ-氨基丁酸（GABA）系统参与癫痫的控制。我们之前的研究表明，在幼鼠中，向黑质内注射γ-乙烯基-GABA（GVG，5-20微克）可强烈抑制氟烷诱导的强直性癫痫发作，但对阵挛性癫痫发作无效。此外，向黑质内注射荷包牡丹碱或蝇蕈醇可消除GVG的抗惊厥作用。在本研究中，我们报告在成年大鼠中，向黑质网状部（SNR）双侧注射GVG（20微克）可显著提高氟烷诱导的阵挛性和强直性癫痫发作的阈值。较低剂量（5和10微克）对成年大鼠癫痫发作没有显著保护作用，但GVG剂量有显著影响。在SNR单侧注射GVG（20微克）不会改变氟烷诱导的癫痫发作阈值。在GVG预处理后向黑质内注射荷包牡丹碱可消除GVG对氟烷诱导的癫痫发作的保护作用，表明GVG的抗惊厥作用很可能是由黑质GABAA受体介导的。在GVG预处理后向黑质内注射蝇蕈醇可显著抑制氟烷诱导的癫痫发作，但两种药物的联合作用不如单独使用GVG强。数据表明GVG可保护成年大鼠免受氟烷诱导的癫痫发作。然而，在成年大鼠中，预防阵挛性和强直性癫痫发作所需的GVG剂量高于幼鼠SNR所需的剂量。
