GLUTAMATE UPTAKE IN SELECTIVELY BRED MICE
GLUTAMATE UPTAKE IN SELECTIVELY BRED MICE
批准号:
2543275
负责人:
Jennifer F. Buckman
金额:
$1.87万
依托单位国家:
美国
项目类别:
财政年份:
1998
资助国家:
美国
项目状态:
未结题
起止时间:
1998-05-25 至
关键词:
alcoholism /alcohol abuse behavioral genetics convulsions drug abuse drug withdrawal electron microscopy ethanol frontal lobe /cortex glutamate transporter hippocampus immunocytochemistry laboratory mouse neurochemistry neurotransmitter metabolism pharmacogenetics protein structure function synaptosomes
中文摘要
戒断性癫痫倾向(WSP)和戒断性癫痫抵抗
(WSR)小鼠选择性繁殖,重复,以显示差异
乙醇处理过程中对处理诱发惊厥(HIC)的敏感性
戒断 通过描述存在的神经化学差异,
在这些线之间,可能阐明基因产物,
与药物依赖风险增加相关(通过
退出的严重性)。 这个项目的目标是描述
WSP和WSR小鼠的谷氨酸摄取,以确定这些类型是否
谷氨酸功能的改变参与了
对HIC的敏感性和抗性。 亲和力和最大L-[3 H]
海马和额叶皮质突触体的谷氨酸摄取将
用生化摄取测定法进行分析。 神经元摄取
突触体也将使用电子显微镜结合
用免疫金免疫细胞化学技术 受试者将
包括WSP和WSR小鼠两个复制系,它们是:(1)乙醇-
(2)未使用乙醇,但惊厥;(3)惊厥-
未接受过治疗,但在急性乙醇后戒断;(4)惊厥和戒断
急性乙醇后;(5)惊厥-幼稚,但在慢性乙醇后退出
乙醇 酗酒是一个突出的社会问题,至少,
部分继承。 本奖学金中提出的实验将
分析与分化相关的遗传和神经化学因素,
易受药物滥用的影响
英文摘要
The Withdrawal Seizure-Prone (WSP) and Withdrawal Seizure-Resistant
(WSR) mice were selectively bred, in replicate, to display differential
susceptibility to handling-induced convulsions (HICs) during ethanol
withdrawal. By characterizing neurochemical differences that exist
between these lines, it may be possible to elucidate gene products
associated with increased risk for becoming drug dependent (measured by
severity of withdrawal). The goal of this project is to characterize
glutamate uptake in WSP and WSR mice to determine whether these types
of alterations in glutamate functioning are involved in conferring
susceptibility and resistance to HICs. Affinity and maximal L-[3H]
glutamate uptake in hippocampal and frontal cortical synaptosomes will
be analyzed with biochemical uptake assays. Neuronal uptake in
synaptosomes will also be assessed using electron microscopy combined
with an immuno-gold immuno-cytochemical technique. The subjects will
include both replicate lines of WSP and WSR mice that are: (1) ethanol-
and convulsion-naive; (2) ethanol-naive, but convulsed; (3) convulsion-
naive, but withdrawn after acute ethanol; (4) convulsed and withdrawn
after acute ethanol; (5) convulsion-naive, but withdrawn after chronic
ethanol. Alcoholism is a prominent social problem that is, at least,
partially inherited. The experiments proposed in this fellowship will
analyze genetic and neurochemical factors associated with differential
susceptibility to drug abuse.
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