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Endocannabinoid modulation of memory

内源性大麻素对记忆的调节

基本信息

批准号：
7459921
负责人：
ARON H LICHTMAN
金额：
$ 27.88万
依托单位：
VIRGINIA COMMONWEALTH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-08-01 至 2011-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7459921
关键词：
Address Agonist Animal Model Area Behavior Behavioral Behavioral Model Brain Brain region CNR1 gene Cannabinoids Catabolism Cognition Cognitive Disruption Endocannabinoids Enzymes Extinction (Psychology)Goals Hippocampus (Brain)In Vitro Knowledge Learning Light Link Mediating Memory Memory impairment Metabolism Mus Personal Satisfaction Pharmaceutical Preparations Phenotype Physiological Play Procedures Process Purpose Rate Receptor Signaling Research Research Personnel Resistance Role SR 141716 Short-Term Memory Signal Transduction Site Structure System Testing Time Wild Type Mouse Work analog anandamide base capsaicin receptor endogenous cannabinoid system fatty acid amide hydrolase forgetting in vivo inhibitor/antagonist interest long term memory morris water maze mouse model object recognition programs receptor reinforcer relating to nervous system research study response

项目摘要

DESCRIPTION (provided by applicant): The discovery of an endocannabinoid system in the brain consisting of cannabinoid CB1 receptors and endocannabinoids (e.g., anandamide and 2-AG) has generated a great deal of interest in understanding the physiological functions of this system. Based on converging in vivo and in vitro evidence this system has been proposed to play an active role in processes that underlie the degradation of memory over time (i.e., forgetting) as well as the suppression of learned behaviors that are no longer reinforced (i.e., extinction). Under normal circumstances, these processes are further hypothesized to facilitate the encoding of new information. The studies proposed in this application will examine the function of this system by blocking endocannabinoid signaling either permanently (i.e., CB1 (-/-) mice) or acutely through the use of the CB1 receptor antagonist SR 141716. Although these approaches can indirectly implicate the involvement of endocannabinoids, the availability of mice in which fatty acid amide hydrolase (FAAH), the primary enzyme responsible for anandamide metabolism, has been genetically deleted (i.e., FAAH (-/-) mice) along with a selective FAAH inhibitor will enable us to determine whether this endocannabinoid plays a role in memory. Additionally, we will investigate the neural substrates and receptor mechanisms of action that underlie endocannabinoid modulation of memory. We will ascertain whether the levels of anandamide and 2-AG are modified by behavioral procedures that are found to be under endocannabinoid tone. Finally experiments will also be conducted to determine whether the mnemonic effects of the cannabinoids are mediated in the hippocampus, a brain region that not only contains CB1 receptors and endocannabinoids, but also is known to play a role in learning and memory. Collectively, these studies will further our understanding of the physiological function of this system as well as bridge the gap between the in vitro and in vivo actions of the endocannabinoid system.

描述（由申请人提供）：发现脑中由大麻素CB 1受体和内源性大麻素（例如，anandamide和2-AG）已经引起了人们对理解该系统的生理功能的极大兴趣。基于体内和体外证据的汇聚，已经提出该系统在记忆随时间退化的基础过程中发挥积极作用（即，遗忘）以及对不再被强化的习得行为的抑制（即，灭绝）。在正常情况下，这些过程被进一步假设为促进新信息的编码。本申请中提出的研究将通过永久地阻断内源性大麻素信号传导（即，CB 1（-/-）小鼠）或通过使用CB 1受体拮抗剂SR 141716急性给药。虽然这些方法可以间接地暗示内源性大麻素的参与，但其中脂肪酸酰胺水解酶（FAAH）（负责大麻素代谢的主要酶）已被遗传缺失的小鼠的可用性（即，FAAH（-/-）小鼠）沿着选择性FAAH抑制剂将使我们能够确定这种内源性大麻素是否在记忆中发挥作用。此外，我们将研究内源性大麻素调节记忆的神经底物和受体作用机制。我们将确定大麻素和2-AG的水平是否被发现在内源性大麻素音调下的行为程序所改变。最后，还将进行实验以确定大麻素的记忆效应是否在海马体中介导，海马体是一个不仅含有CB 1受体和内源性大麻素的大脑区域，而且已知在学习和记忆中发挥作用。总的来说，这些研究将进一步加深我们对该系统的生理功能的理解，并弥合内源性大麻素系统的体外和体内作用之间的差距。

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）

Pharmacological evaluation of the natural constituent of Cannabis sativa, cannabichromene and its modulation by Δ(9)-tetrahydrocannabinol.

DOI：
10.1016/j.drugalcdep.2010.05.019
发表时间：
2010-11-01
期刊：
DRUG AND ALCOHOL DEPENDENCE
影响因子：
4.2
作者：
DeLong, Gerald T.;Wolf, Carl E.;Poklis, Alphonse;Lichtman, Aron H.
通讯作者：
Lichtman, Aron H.

The cannabinoid CB(1) receptor antagonist CE prolongs spatial memory duration in a rat delayed radial arm maze memory task.

大麻素 CB(1) 受体拮抗剂 CE 可延长大鼠延迟径向臂迷宫记忆任务的空间记忆持续时间。

DOI：
10.1016/j.ejphar.2008.06.049
发表时间：
2008
期刊：
European journal of pharmacology
影响因子：
5
作者：
Wise,LauraE;Iredale,PhilipA;Lichtman,AronH
通讯作者：
Lichtman,AronH

Combination of rimonabant and donepezil prolongs spatial memory duration.

利莫那班和多奈哌齐的组合可延长空间记忆持续时间。

DOI：
10.1038/sj.npp.1301297
发表时间：
2007
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
0
作者：
Wise,LauraE;Iredale,PhilipA;Stokes,ReneJ;Lichtman,AronH
通讯作者：
Lichtman,AronH

Lack of behavioral sensitization after repeated exposure to THC in mice and comparison to methamphetamine.

小鼠反复接触 THC 后缺乏行为敏感性，并与甲基苯丙胺进行比较。