Influence of drugs of abuse on neuronal morphology

描述：反复服用精神兴奋剂药物，如 安非他明或可卡因，产生持续的行为和神经生物学 被认为会导致长期后遗症的适应 包括耐受、敏感、依赖和成瘾。 一种形式的神经行为适应牵连成瘾是代表 行为敏感化现象，即过去的药物暴露， 使个人对精神刺激和激励过敏， 药物的激励作用。该应用程序的总体目标是更好地 了解反复暴露的长期神经生物学后果 精神兴奋剂药物，这些在行为发展中发挥的作用 敏感性，以及它们对成瘾的影响。更具体地说，我们有 最近发现，反复使用安非他明或可卡因治疗， 树突和树突棘结构的持续变化， 位于脑桥核和前额叶皮层的神经元，这两个大脑区域 在调节药物奖赏中起重要作用。这些发现表明 暴露于精神兴奋剂药物改变了突触连接的模式， 这些大脑区域，大概也改变了这个神经元的功能， 电路本申请的具体目的是进一步表征本发明的化合物。 精神兴奋剂药物改变大脑奖赏中神经回路的能力 区域（使用高尔基技术），并确定这些结构是否 适应与心理敏感性的发展有关。在一个 在一系列实验中，我们将使用各种已知的程序来增加或 降低行为敏感化的强度或持久性， 有证据表明，结构性适应 与行为现象共同变化。在其他实验中，我们将获得 关于精神兴奋剂药物诱导的确切位点的更详细的信息 中等多刺神经元和锥体细胞上的棘密度的变化（即，是 结构变化局限于树突树的一部分），以及是否 其他细胞群也受到影响。此外，我们将确定 药物自我给药经验是否对树突状细胞产生影响 结构类似于实验者给药的药物， 自我服用可卡因的暴露程度， 摄入量的增加和形态学上的适应。最后，在去年， 我们将扩大调查范围，研究 药物诱导的可塑性对其他形式的经验依赖性的影响 可塑性具体来说，我们将测试是否暴露于精神兴奋剂 药物在生命的某个阶段限制了受影响的大脑区域的能力， 在以后的生活中经历结构适应，作为变化的结果， 环境条件或与脑损伤恢复相关。

DESCRIPTION: The repeated administration of psychostimulant drugs, such as amphetamine or cocaine, produces persistent behavioral and neurobiological adaptations that are thought to contribute to the long-term sequelae associated with drug abuse, including tolerance, sensitization, dependence and addiction. One form of neurobehavioral adaptation implicated in addiction is represented by the phenomenon of behavioral sensitization, whereby past drug exposure renders individuals hypersensitive to the psychomotor activating and incentive motivational effects of drugs. The overall aim of this application is to better understand the long-term neurobiological consequences of repeated exposure to psychostimulant drugs, the role these play in the development of behavioral sensitization, and their implications for addiction. More specifically, we have recently found that repeated treatment with amphetamine or cocaine produces persistent changes in the structure of dendrites and dendritic spines on neurons in the nucleus accumbens and prefrontal cortex, two brain regions prominently implicated in mediating drug reward. These findings suggest that exposure to psychostimulant drugs alters patterns of synaptic connectivity in these brain regions, presumably also altering the function of this neural circuitry. A specific aim of this application is to further characterize the ability of psychostimulant drugs to alter neural circuitry in brain reward regions (using the Golgi technique) and to determine whether these structural adaptations are related to the development of psychomotor sensitization. In one series of experiments we will use a variety of procedures known to increase or decrease the strength or persistence of behavioral sensitization to accumulate converging evidence regarding the extent to which structural adaptations co-vary with the behavioral phenomenon. In other experiments we will acquire more detailed information about the exact locus of psychostimulant drug-induced changes in spine density on medium spiny neurons and pyramidal cells (i.e., are structural changes confined to one portion of the dendritic tree), and whether other cell populations are also affected. In addition, we will determine whether drug self-administration experience produces effects on dendritic structure similar to those seen with experimenter-administered drug, and the relationship between the degree of exposure to self-administered cocaine, escalation of intake and morphological adaptations. Finally, in the last year of the award period we will expand the scope of our investigations to study the implications of drug-induced plasticity for other forms of experience-dependent plasticity. Specifically, we will test whether exposure to psychostimulant drugs at one point in life limits the ability of the affected brain regions to undergo structural adaptations later in life, as a consequence of changes in environmental condition or in association with recovery from brain damage.