COCAINE IMPACT ON PLASTICITY & DENDRITE MORPHOLOGY

可卡因对可塑性的影响

• 批准号: 7389841
• 负责人: Terry E. Robinson
• 金额: $ 21.26万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-25 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7389841
• 关键词: Adult; Amphetamines; Animal Housing; Animal Model; Behavior; Behavioral; Brain; Brain region; Breeding; Climacteric; Clinical; Cocaine; Cocaine Abuse; Complex; Condition; Control Animal; Data; Dendrites; Dendritic Spines; Dorsal; Dose; Drug usage; Environment; Excitatory Synapse; Exposure to; Future; Gene Expression; Genes; Genetic Predisposition to Disease; Hippocampus (Brain); Learning; Life; Life Experience; Mediating; Molecular; Morphology; Nicotine; Nucleus Accumbens; Parietal Lobe; Pattern; Pharmaceutical Preparations; Population; Predisposition; Prefrontal Cortex; Rattus; Relapse; Reporting; Research Personnel; Saline; Standards of Weights and Measures; Structure; Synapses; Synaptic plasticity; Thinking; Time; Ventral Striatum; Withdrawal Symptom; addiction; behavior change; behavioral sensitization; brain behavior; density; drug of abuse; experience; neural circuit; neurogenesis; neuropsychological; psychologic; psychostimulant; response

Cocaine Impact on Plasticity & Dendrite Morphology: Interaction with Environmental Complexity One of the most compelling examples of experience-dependent behavioral plasticity, whereby experience at one period in life changes behavior for a lifetime, is addiction. The propensity of addicts to relapse, even months to many years after the discontinuation of drug use,and long after withdrawal symptoms have subsided, provides stark evidence that drug use has long lasting consequences for behavior and psychological function. Similarly, very long-lasting changes in brain and behavior have been found in animal models, for example, following sensitization. Persistent experience-dependent changes in behavior and synaptic organization are presumably due to the effects of drugs and other experiences acting via coordinated actions on a variety of plasticity-related genes, and perhaps by influencing neurogenesis. Indeed, there is now considerable evidence that drugs of abuse usurp many of the same cellular and molecular mechanisms responsible for experience-dependent plasticity. This raises the hypothesis that changes in synaptic organization produced by experience may interact with those produced by exposure to drugs of abuse. The overall aim of this project is to explore the interaction between the effects of exposure to a drug of abuse, cocaine, and the effects of another life experience (living in a relatively complex environment), on the expression of key plasticity-related genes and on adult neurogenesis, in two genetically-distinct populations of rats that vary in their susceptibility to cocaine. Studies to date support the hypothesis that exposure to psychostimulant drugs may,under some circumstances and in some brain regions, saturate the potential for future plasticity (or produce "metaplasticity") and thus occlude the ability of subsequent experiences to induce molecules necessary for synaptic reorganization. The hypothesis that exposure to psychostimulant drugs may limit the potential for future plasticity in response to changes in environmental condition has important clinical implications. If true, it would suggest that the repeated use of some drugs of abuse might limit the ability to adapt positively to changes in environmental circumstances. Thus, some of the neuropsychological deficits seen in addicts could be due to limits on synaptic plasticity imposed by past druguse.

CO2对塑性和枝晶形态的影响：与环境复杂性的相互作用 经验依赖性行为可塑性的最引人注目的例子之一， 生活中某个时期的经历会改变一生的行为，这就是成瘾。上瘾者的倾向 复发，甚至在停药后数月至数年，以及停药后很长时间 症状已经消退，提供了明确的证据表明，吸毒对行为有长期持久的影响。 心理功能。同样，在大脑和行为中发现了非常持久的变化， 动物模型，例如致敏后。持续的经验依赖性行为变化 和突触组织可能是由于药物和其他经验的影响， 协调行动的各种可塑性相关基因，并可能通过影响神经发生。 事实上，现在有相当多的证据表明，滥用药物篡夺了许多相同的细胞和神经系统。 负责经验依赖性可塑性的分子机制。这就提出了一个假设， 由经验引起的突触组织的变化可能与暴露于 滥用药物。 这个项目的总体目标是探索暴露于药物的影响之间的相互作用 滥用，可卡因，以及另一种生活经历（生活在相对复杂的环境中）的影响， 关键可塑性相关基因的表达和成人神经发生，在两个遗传上不同的 对可卡因的敏感性各不相同的老鼠种群。迄今为止的研究支持这样一种假设， 在某些情况下，在某些脑区，暴露于精神兴奋剂药物可能会使大脑皮层饱和， 潜在的未来可塑性（或产生“超可塑性”），从而闭塞了随后的能力， 诱导突触重组所必需的分子。假设暴露于 精神兴奋剂药物可能会限制未来可塑性的潜力，以应对环境的变化， 具有重要的临床意义。如果这是真的，这将表明，重复使用某些药物， 虐待可能会限制积极适应环境变化的能力。因此， 成瘾者的神经心理缺陷可能是由于过去的记忆对突触可塑性的限制， 吸毒