Velísková J, Velísek L, Nunes M L, Moshé S L
Department of Neurology, Albert Einstein College of Medicine, Bronyx, NY, USA.
Eur J Pharmacol. 1996 Aug 8;309(2):167-73. doi: 10.1016/0014-2999(96)00341-x.
GABAergic (gamma-aminobutyric acid) transmission in the substantia nigra pars reticulata is critical for seizure control. We tested the hypothesis that there is a differential regional distribution and functionality of nigral GABAA receptor sites that is developmentally regulated. In adult rats, we determined the effects on flurothyl seizures of (Z)-3-[(aminoiminomethyl)thio]prop-2-enoic acid (ZAPA, a presumed agonist of the low-affinity GABAA receptor site), bicuculline (an antagonist of the low-affinity GABAA receptor site) and gamma-vinyl-GABA (a GABA-transaminase inhibitor), infused bilaterally in anterior or posterior substantia nigra pars reticulata. ZAPA infusions (8 micrograms) were anticonvulsant in anterior substantia nigra but proconvulsant in posterior substantia nigra. Bicuculline infusions (100 ng) were proconvulsant in anterior substantia nigra but ineffective in posterior substantia nigra. An anticonvulsant dose of gamma-vinyl-GABA, when infused in anterior substantia nigra, was proconvulsant when infused in posterior substantia nigra. In 15 day old rats, the effects of ZAPA, were biphasic: 2 micrograms was anticonvulsant while 8 micrograms was proconvulsant. There was no regional specificity. The data suggest that with maturation there is functional segregation of specific GABAA receptor subtypes involved in substantia nigra-mediated seizure control.
黑质网状部的γ-氨基丁酸（GABAergic）能传递对癫痫控制至关重要。我们检验了这样一个假说，即黑质GABAA受体位点存在发育调控的差异性区域分布和功能。在成年大鼠中，我们测定了双侧注入前或后黑质网状部的（Z）-3-[(氨基亚氨甲基)硫代]丙烯酸（ZAPA，一种推测的低亲和力GABAA受体位点激动剂）、荷包牡丹碱（低亲和力GABAA受体位点拮抗剂）和γ-乙烯基-GABA（一种GABA转氨酶抑制剂）对氟烷性癫痫发作的影响。注入ZAPA（8微克）在前黑质有抗惊厥作用，但在后黑质有促惊厥作用。注入荷包牡丹碱（100纳克）在前黑质有促惊厥作用，但在后黑质无效。抗惊厥剂量的γ-乙烯基-GABA注入前黑质时具有抗惊厥作用，但注入后黑质时则具有促惊厥作用。在15日龄大鼠中，ZAPA的作用是双相的：2微克有抗惊厥作用，而8微克有促惊厥作用。不存在区域特异性。数据表明，随着成熟，参与黑质介导的癫痫控制的特定GABAA受体亚型存在功能分离。
