COCAINE IMPACT ON PLASTICITY & DENDRITE MORPHOLOGY

可卡因对可塑性和树枝晶形态的影响：与环境复杂性的交互作用 依赖经验的行为可塑性的最引人注目的例子之一， 生活中某一阶段的经历会改变一生的行为，这就是上瘾。吸毒者的嗜好 复发，甚至在停止使用药物后数月至数年，并在戒毒后很长时间 症状已经消退，这为吸毒对行为产生长期的后果提供了确凿的证据 和心理功能。同样，在大脑和行为方面也发现了非常持久的变化 动物模型，例如，在敏化之后。持续的依赖经验的行为变化 和突触组织可能是由于药物的影响和其他通过 协调各种可塑性相关基因的作用，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，滥用药物侵占了许多相同的细胞和 依赖经验的可塑性的分子机制。这提出了一种假设，即 由经验产生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接触药物的影响之间的相互作用。 滥用、可卡因和另一种生活经历(生活在相对复杂的环境中)的影响， 两种不同遗传方式的成体神经发生中关键可塑性相关基因的表达 对可卡因易感性不同的老鼠种群。迄今为止的研究支持这样一种假设 在某些情况下，在某些大脑区域，接触精神刺激性药物可能会使大脑饱和 潜在的未来可塑性(或产生“元可塑性”)，从而阻碍了后续的能力 诱导突触重组所需分子的经验。假设暴露在空气中 精神刺激药物可能会限制未来因环境变化而发生可塑性的可能性 病情具有重要的临床意义。如果是真的，这将表明重复使用一些药物 滥用可能会限制积极适应环境环境变化的能力。因此，其中一些 成瘾者的神经心理缺陷可能是由于过去对突触可塑性的限制 吸毒者。

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.