Regional specificity of ethanol and NMDA action in brain revealed with FOS-like immunohistochemistry and differential routes of drug administration
Regional specificity of ethanol and NMDA action in brain revealed with FOS-like immunohistochemistry and differential routes of drug administration
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DOI：
10.1097/00000374-200111000-00014
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发表时间：
2001-11-01
影响因子：
3.2
通讯作者：
Breese, GR
中科院分区：
文献类型：
--
作者：
Knapp, DJ;Braun, CJ;Breese, GR
背景：乙醇对脑内NMDA受体功能的抑制被认为是乙醇的一个重要作用。研究乙醇抑制NMDA受体反应在体内，这些药物在大脑中的相互作用后，不同途径的管理进行了研究，通过使用转录因子Fos蛋白的表达，以遵循NMDA受体激活和乙醇抑制这种response.Methods：诱导Fos样免疫反应（Fos-LI）在38个区域的大鼠脑2小时后，测定与NMDA，乙醇，或两者兼而有之。为了确定腹部药物作用对Fos诱导的相对贡献，大鼠接受腹膜内（ip）或胃内（IG）EtOH和ip或静脉内（iv）NMDA。结果：在38个前脑区中，ip和iv NMDA（125 mg/kg ip或60 mg/kg IG）分别在13个和32个脑区诱导Fos-LI。这些影响发生时没有引起强直阵挛性癫痫发作活动，静脉注射NMDA后，额叶，前额，扣带回皮质，视上核，前外侧隔，齿状回强烈。对于EtOH，在中央杏仁核、终纹背外侧床核、Edinger-Westphal核和室旁下丘脑中发现显著的Fos-LI诱导。尽管ip和IG EtOH诱导了这些区域的Fos-LI，但EtOH的主要作用是分别在13个（ip）中的8个和32个（IG）中的27个NMDA阳性区域中阻断NMDA诱导的Fos-LI，包括压后、扣带回和内侧前额叶皮质、中央杏仁核和顶盖带。这些结果提供了新的证据的区域特异性功能的相互作用，乙醇对NMDA受体在体内。此外，这些结果支持努力，以确定大脑区域的特定目标乙醇和乙醇诱导的基因表达的变化。
Background: Inhibition of NMDA receptor function in brain is believed to be an important action of ethanol (EtOH). To investigate EtOH inhibition of NMDA receptor responses in vivo, the interaction of these agents in brain after different routes of administration were investigated by using transcription factor Fos protein expression to follow NMDA receptor activation and EtOH inhibition of this response.Methods: The induction of Fos-like immunoreactivity (Fos-LI) in 38 regions of the rat brain was measured 2 hr after treatment with NMDA, EtOH, or both. To determine the relative contribution of abdominal drug effects on Fos induction, rats received either intraperitoneal (ip) or intragastric (ig) EtOH and ip or intravenous (iv) NMDA. Rats received EtOH (2.5 g/kg ip or 4 g/kg ig) or vehicle 15 min before NMDA (125 mg/kg ip or 60 mg/kg iv) or vehicle.Results: For the 38 forebrain regions examined, ip and iv NMDA significantly induced Fos-LI in 13 and 32 regions, respectively. These effects occurred without elicitation of tonic-clonic seizure activity and were strong after iv NMDA in the frontal, prefrontal, and cingulate cortices, supraoptic nucleus, anterior lateral septum, and dentate gyrus. For EtOH, prominent Fos-LI induction was found in the central amygdala, dorsolateral bed nucleus of the stria terminalis, Edinger-Westphal nucleus, and paraventricular hypothalamus. Despite ip and ig EtOH induction of Fos-LI in these regions, the major effect of EtOH was to block NMDA-induced Fos-LI in 8 of 13 (ip) and 27 of 32 (ig) of the NMDA-positive regions, respectively, including retrosplenial, cingulate, and medial prefrontal cortices, central amygdala, and taenia tecta.Conclusions: These results provide new evidence for the regionally specific functional interactions of EtOH on NMDA receptors in vivo. Moreover, these results support efforts to identify brain region-specific targets for EtOH and EtOH-induced changes in gene expression.