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Galnon modulation of memory

记忆的伽农调制

基本信息

批准号：
6547402
负责人：
JOHN Kenneth ROBINSON
金额：
$ 7.53万
依托单位：
STATE UNIVERSITY NEW YORK STONY BROOK
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-09-01 至 2004-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6547402
关键词：
alpha benzopyrone anticholinergic agent behavior test blood brain barrier cerebral ventricles clinical research dosage galanin hippocampus histology inhibitor /antagonist laboratory rat memory microinjections neuropeptide receptor neuropharmacology stereotaxic techniques

项目摘要

Galanin is a neuropeptide that play an important role in memory formation and may contribute to the cognitive deficits in Alzheimer's disease. Therefore, galanin receptor antagonists may be for drugs for treating memory loss in Alzheimer's disease. The goal of the proposed studies is to determine whether a novel non-peptide galanin receptor ligand, galnon, exhibits similar disruptive effects on memory in rats as galanin. In the initial experiments, galnon will be administered into the lateral ventricle and into the ventral hippocampus to establish a dose- response relationship and to determine the extent that the effects of galnon can be localized to the ventral hippocampus (Aim 1). Next, galanin antagonists will be co-administered with galnon into these sites to confirm that the performance disruption of the memory tasks is mediated by galanin receptors (Aim 2). Finally, the potential for galnon to cross the blood-brain barrier and produce effects on memory will be assessed by administering it systemically (Aim 3). Successful demonstration of mnemonic effects of galnon similar to those of galanin will lead to a comprehensive program to modify galnon's chemical structure to produce a galanin antagonist that crosses the blood-brain barrier, is stable in vivo, and that posses memory-enhancing properties.

甘丙肽是一种神经肽，在记忆形成中发挥重要作用，可能与阿尔茨海默病的认知缺陷有关。因此，甘丙肽受体拮抗剂可能是治疗阿尔茨海默病记忆丧失的药物。拟议研究的目的是确定一种新的非肽Galanin受体配体Galnon是否表现出与Galanin类似的对大鼠记忆的干扰作用。在最初的实验中，Galnon将进入侧脑室和腹侧海马区，以建立剂量-反应关系，并确定Galnon的作用可局限于腹侧海马区的程度(目标1)。接下来，甘丙肽拮抗剂将与甘丙肽一起进入这些部位，以确认记忆任务的执行中断是由甘丙肽受体介导的(目标2)。最后，将通过系统地给药来评估Galnon跨越血脑屏障并对记忆产生影响的可能性(目标3)。Galnon类似于Galanin的助记作用的成功展示将导致一个全面的计划来修改Galnon的化学结构，以生产一种跨越血脑屏障、在体内稳定并具有增强记忆特性的Galanin拮抗剂。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Intracerebroventricular administration of galanin decreases free water intake and operant water reinforcer efficacy in water-restricted rats.

脑室内给予甘丙肽可降低限水大鼠的自由水摄入量和操作性水强化剂功效。

DOI：
10.1016/j.npep.2005.01.006
发表时间：
2005
期刊：
Neuropeptides.
影响因子：
0
作者：
Brewer,Ariel;Langel,Ulo;Robinson,JohnK
通讯作者：
Robinson,JohnK

Galanin and perseveration.

甘丙肽和毅力。

DOI：
10.1016/j.brainres.2005.01.103
发表时间：
2005
期刊：
Brain research.
影响因子：
0
作者：
Echevarria,DavidJ;Brewer,Ariel;Bushell,Georgia;Manuzon,Honeyleen;Langel,Ulo;Robinson,JohnK
通讯作者：
Robinson,JohnK

Galanin stimulation of feeding is blocked by the addition of a response requirement.

通过增加反应要求来阻止甘丙肽对进食的刺激。