The Amygdala, Individual Differences, and Conditioned Hyperactivity

杏仁核、个体差异和条件性多动症

• 批准号: 7194722
• 负责人: Mary Eileen Cain
• 金额: $ 7.12万
• 依托单位: KANSAS STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-30 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7194722
• 关键词: amphetamines; amygdala; conditioning

DESCRIPTION (provided by applicant): Numerous studies suggest that people who prefer novel or arousing stimulation (e.g. high sensation- seekers) use drugs more frequently than low sensation seekers. Thus, high sensation-seekers may be predisposed biologically to find both novel stimuli and drugs to be more rewarding than low sensation- seekers. The long-term goal of this research is to determine if individuals who prefer novel and arousing stimuli share a common neuroanatomical mechanism using an animal model. Rats that are highly active in a novel environment (high responders) are more sensitive to amphetamine-induced locomotor activity and self-administer more amphetamine compared to rats that are relatively inactive (low responders). Previous research has demonstrated that inactivation of the central nucleus of the amygdala (ACe) reduces amphetamine self-administration only in high responder rats. The overall mechanistic framework for the proposed set of experiments is based on the role of the ACe in regulating arousal due to its extensive cortical and subcortical projections. The hypothesis is that the ACe is more active in high responder rats compared to low responder rats. The effects of inactivation of the ACe on subsequent amphetamine- induced locomotor activity will be measured to determine if the ACe contributes to the increased sensitivity of high responder rats to amphetamine-induced locomotor activity. Further, the amount of conditioned activity in an amphetamine-associated environment will be measured to determine if the ACe contributes to conditioned activity and if high responder and low responder rats differ in conditioned activity. In addition, the amount of c-fos expression will be measured in the ACe to determine if the ACe has greater activity in high responder rats. The findings of these experiments are intended to advance the understanding of vulnerability for stimulant abuse, and will potentially lead to better prevention and treatment interventions.

描述（由申请人提供）：大量研究表明，喜欢新颖或引起刺激的人（例如，寻求刺激的人）比寻求低感觉的人更频繁地使用药物。因此，在生物学上可能会倾向于发现新颖的刺激和药物比低感觉寻求者更有意义。这项研究的长期目标是确定喜欢新颖和诱发刺激的个体是否使用动物模型共享一种常见的神经解剖学机制。与相对不活跃的大鼠相比，在新型环境中高度活跃的大鼠对苯丙胺诱导的运动活性和自动化更多的苯丙胺更敏感。先前的研究表明，杏仁核（ACE）中央核的失活仅在高响应者大鼠中降低了苯丙胺自我给药。拟议的一组实验的总体机械框架是基于ACE在调节唤醒中的作用，这是由于其广泛的皮质和皮层投影。假设是，与低响应者大鼠相比，ACE在高响应者大鼠中更为活跃。将测量ACE失活对随后的苯丙胺诱导的运动活性的影响，以确定ACE是否有助于高响应者对苯丙胺诱导的运动运动活性的敏感性。此外，将测量与苯丙胺相关环境中的条件活性量，以确定ACE是否有助于条件活动，以及高响应者和低响应者大鼠的条件活性不同。另外，将在ACE中测量C-FOS表达的量，以确定ACE在高响应者大鼠中是否具有更大的活性。这些实验的发现旨在提高人们对刺激滥用的脆弱性的理解，并有可能导致更好的预防和治疗干预措施。