Stress & Vulnerability to Drug Abuse: Neural Correlates

描述(由申请人提供)：个人差异很大 有尝试滥用药物并对其上瘾的倾向。 一些人可能会将寻求毒品作为寻求感觉或冒险行为的一个方面。 其他人这样做可能是因为社会或心理压力。目的 这项建议是为了研究这些个体的神经生物学基础。 对滥用药物的易感性存在差异。基本的前提是 遗传、发育和环境因素的组合导致 脆弱性的差异在大脑中表现出来，并且需要 在那个级别上理解。相关基因的主要表达部位是 很可能是在调节情绪大脑回路的背景下 对压力和环境的反应，这变得不受控制 在上瘾和情绪障碍方面。 为了研究药物个体差异的神经元基础 虐待，这一建议依赖于一种行为模型，该模型区分 是耸人听闻的或从那些不是的地方寻求新鲜感。这些 寻求感觉的动物学习给药，如安非他明，许多 尽管药物对他们有同样的回报，但速度更快。我们计划 描述不同基因在大鼠体内的表达模式 感觉寻求行为的表型。我们计划专注于与压力相关的 基因，并确定可能存在的独特的神经元表型 与寻求感觉和吸毒行为有关。然后我们计划使用 一个心理社会压力模型，社会失败感，来研究这样的影响 吸毒行为及其相关因素获得率的研究 不同基因在这些不同的情绪回路中的表达模式 动物。这些研究应该会开始让我们一窥基因的表达方式 不同虐待倾向的人的大脑回路可能也不同 药物，以及社会压力如何影响这些系统，进一步修改 并导致不同的行为反应。

DESCRIPTION (provided by applicant): Individuals vary significantly in their propensity to experiment with drugs of abuse and to become addicted to them. Some may seek drugs as an aspect of sensation seeking or risk taking behavior. Others may do so as a result of social or psychological stress. The purpose of this proposal is to investigate the neurobiological basis for these individual differences in vulnerability to abusing drugs. The basic premise is that the combination of genetic, developmental and environmental factors that lead to differences in vulnerability is expressed in the brain, and needs to be understood at that level. The primary site of expression of relevant genes is likely in the context of the emotional brain circuits that regulate responsiveness to stress and to the environment, and that become dysregulated in addiction and in mood disorders. In order to investigate the neuronal basis of individual differences in drug abuse, this proposal relies on a behavioral model that distinguishes rats that are sensation or novelty-seeking from those that are not. These sensation-seeking animals learn to administer drugs, such as amphetamine, much more rapidly although the drugs are equally rewarding to them. We plan to characterize the patterns of gene expression in rats that exhibit different phenotypes of sensation-seeking behavior. We plan to focus on stress related genes and determine the possible presence of unique neuronal phenotypes associated with sensation-seeking and drug-taking behavior. We then plan to use a model of psychosocial stress, social defeat, to study the impact of such stress on the rate of acquisition of drug taking behavior and the associated patterns of gene expression in the emotional circuits of these differing animals. These studies should begin to give us a glimpse of how gene expression and brain circuits may differ in individuals with differing tendencies to abuse drugs, and how social stress can impact on these systems, further modifying them and leading to distinctive behavioral responses.