EXPRESSION OF C-FOS MESSENGER-RNA IN ACUTE AND KINDLED COCAINE SEIZURES IN RATS

EXPRESSION OF C-FOS MESSENGER-RNA IN ACUTE AND KINDLED COCAINE SEIZURES IN RATS
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DOI:
10.1016/0006-8993(92)90322-z
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发表时间:
1992-06-05
期刊:
影响因子:
2.9
通讯作者:
NAKAJIMA, T
NAKAJIMA, T
中科院分区:
医学3区
文献类型:
--
作者:
CLARK, M;POST, RM;NAKAJIMA, T

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对脑切片进行c-fos mRNA的原位杂交,这些脑切片(a)来自急性可卡因诱导癫痫发作后的大鼠或注射生理盐水的对照组,(B)来自首次可卡因点燃癫痫发作后的大鼠,以及来自尚未发生可卡因点燃癫痫发作的大鼠(但暴露于与那些确实表现出惊厥的大鼠相同数量的可卡因)和注射生理盐水的对照组。在可卡因诱导的急性癫痫发作或药物点燃后的动物中观察到c-fos mRNA表达增加。可卡因(65 mg/kg)后经历急性癫痫发作的大鼠显示海马齿状回和嗅球中c-fos mRNA的表达显著增加。在其他几个边缘皮质区域以及纹状体和下丘脑腹内侧核(VMH)中也观察到增加。在每天注射初始亚惊厥剂量的可卡因盐酸盐(40毫克/公斤)的大鼠中,可卡因点燃癫痫发作诱导c-fos mRNA在与急性可卡因诱导癫痫发作相同的脑区升高,唯一例外的是VMH。这些发现不仅表明边缘系统,皮质和纹状体结构在可卡因诱导的癫痫发作的参与,但也提出了可能性,在原癌基因c-fos的改变及其随后对基因表达的影响可能发挥作用的神经兴奋性的变化与可卡因诱导的点燃。
In situ hybridization for c-fos mRNA was performed on brain sections (a) from rats after an acute cocaine-induced seizure or from saline-injected controls and (b) from rats after their first cocaine-kindled seizure, as well as from rats that had not yet developed cocaine-kindled seizures (but were exposed to the same amount of cocaine as those that did exhibit convulsions) and from saline-injected controls. Increased expression of c-fos mRNA was observed in animals demonstrating cocaine-induced seizures acutely or following pharmacological kindling. Rats that experienced acute seizures after cocaine (65 mg/kg) showed pronounced increase in expression of c-fos mRNA in the dentate gyrus of the hippocampus and olfactory bulb. Increases were also observed in several other limbic cortical regions, as well as the striatum and ventromedial hypothalamic nucleus (VMH). In rats that were injected daily with an initially subconvulsive dose of cocaine-HCI (40 mg/kg), the cocaine-kindled seizures induced elevations in c-fos mRNA in the same brain regions as with an acute cocaine-induced seizure with the single exception of the VMH. These findings not only suggest the involvement of limbic, cortical and striatal structures in the cocaine-induced seizure, but also raise the possibility that alterations in the proto-oncogene c-fos and its subsequent impact on gene expression could play a rol in the changes in neural excitability associated with cocaine-induced kindling.