Molecular Cognition of Addiction

成瘾的分子认知

基本信息

批准号：
7880589
负责人：
STEPHAN G ANAGNOSTARAS
金额：
$ 29.98万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-30 至 2012-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7880589
关键词：
Abstinence Accidents Acquired Immunodeficiency Syndrome Affect Amygdaloid structure Behavior Behavioral Behavioral Paradigm Brain Calcium Calcium/calmodulin-dependent protein kinase Calmodulin Cessation of life Chronic Cocaine Cognition Corpus striatum structure Crime Cues Dependence Development Drug Addiction Drug Metabolic Detoxication Drug effect disorder Drug usage Drug user Exposure to Genetic Goals Health Hippocampus (Brain)Homelessness Imprisonment Injection of therapeutic agent Learning Lesion Light Liver diseases Malignant Neoplasms Measures Mediating Medical Memory Modeling Molecular Molecular Biology Mus Neurobiology Neurons Pathway interactions Pharmaceutical Preparations Phosphotransferases Plague Poverty Process Productivity Property Prosencephalon Psychological reinforcement Recruitment Activity Relapse Role Self Administration Short-Term Memory Specificity Staging Structure Synaptic plasticity System Time Translations Violence Withdrawal addiction behavioral sensitization calmodulin-dependent protein kinase II cost craving drug of abuse drug reinforcement effective therapy genetic manipulation memory acquisition neuroadaptation preference relating to nervous system response social

项目摘要

DESCRIPTION (provided by applicant): Both memory and addiction produce long-lasting changes in behavior and result in chronic neural adaptations in response to repeated neural activity. It is therefore likely that memory and addiction recruit some of the same molecular mechanisms of synaptic plasticity in the same neural structures. In the present proposal, we explore the parallels between addiction and memory by examining the impact of genetic and anatomical manipulations known to affect memory on addiction-related behavioral plasticity. In a simple behavioral paradigm in mice we can rapidly quantify psychomotor sensitization to repeated cocaine injections, as well as the conditioned response to cues associated with cocaine administration, the contextual control over the expression of cocaine sensitization, and conditioned place preference induced by cocaine. First, we use this paradigm to evaluate the role of the hippocampus and amygdala in addiction-related memory. Second, we use inducible and region-specific disruption of calcium/calmodulin- dependent protein kinase II (CaMKII), a criticial kinase in memory formation, in addiction. Finally, we examine the role of calcium calmodulin in addiction. A benefit of using modern genetic manipulation is the ability to better localize key neuroadaptations through disruption of dendritic translation, and inducible region-specific disruption of alpha-CaMKI in the forebrain and striatum. The inducible and reversible molecular manipulations we propose, post-induction disruption of CaMKII or calcium calmodulin, actually have the potential to reverse sensitization to cocaine and related memories. Taken together, these studies will evaluate the parallels between memory and addiction-related behavioral plasticity and shed considerable light on whether manipulations of memory will prove useful in the treatment of addiction.Project Narrative Addiction is a major social and medical problem affecting millions of compulsive drug users. In the present proposal we examine the relationship between memory and addiction at the level of the brain. If memory and addiction prove to be highly related, disruptions of memory may prove highly useful in the treatment of addiction.

描述（由申请人提供）：记忆和成瘾都会导致行为的长期变化，并导致慢性神经适应性，以响应重复的神经活动。因此，记忆和成瘾很可能募集了相同神经结构中突触可塑性的某些分子机制。在本提案中，我们通过检查已知影响记忆对成瘾相关行为可塑性的遗传和解剖学操纵的影响，探讨成瘾和记忆之间的相似之处。在小鼠中的简单行为范式中，我们可以快速量化对可卡因注射重复的心理运动的敏感性，以及对可卡因给药相关的提示的条件反应，对可卡因敏化表达的上下文控制，以及可卡因诱导的有条件的位置偏好。首先，我们使用此范式来评估海马和杏仁核在成瘾相关记忆中的作用。其次，我们使用钙/钙调蛋白依赖性蛋白激酶II（CAMKII）的诱导和特定区域特异性破坏，这是一种记忆形成中的批评激酶。最后，我们研究了钙钙调蛋白在成瘾中的作用。使用现代遗传操作的一个好处是能够通过破坏树突转换来更好地定位关键神经适应，以及对前脑和纹状体中alpha-Camki的诱导区域特异性破坏。我们提出的诱导和可逆分子操作，CAMKII或钙钙调蛋白的诱导后破坏实际上有可能反向可卡因和相关记忆。综上所述，这些研究将评估记忆与成瘾相关的行为可塑性之间的相似之处，并大量了解记忆的操纵是否会在对待成瘾的治疗中有用。项目叙事成瘾是影响数百万强迫性吸毒者的主要社会和医学问题。在本提案中，我们检查了大脑水平上记忆与成瘾之间的关系。如果记忆和成瘾被证明是高度相关的，则记忆的中断可能在成瘾治疗中非常有用。