Adolescent Nicotine Exposure and Adult Cognitive Processes in Rats

描述（由申请人提供）：最近的研究表明，青少年药物暴露会导致大脑生理学、大脑奖励系统、对后期成瘾的易感性和简单行为的长期变化。本应用程序中提出的研究涉及一个用于研究大鼠复杂认知过程的连续模式学习范式，该范式严格模仿用于研究人类高级认知功能的非语言范式。这种连续模式学习方法已经证明青少年尼古丁暴露会导致成年大鼠的认知功能障碍。我们建议继续这方面的研究，以调查青少年暴露于尼古丁产生的认知缺陷的程度和性质，使用该模型系统研究大鼠复杂认知过程中涉及的认知和神经系统的功能和功能障碍。拟议的研究将使用连续模式学习范式来实现几个具体目标，以实现研究的总体目标：第一个具体目标是通过初步研究中确定的参数进行剂量-反应研究，以调查青少年尼古丁暴露对成人认知过程的剂量-反应效应。第二个具体目标是描述青少年接触尼古丁对成人认知过程的影响的性质，并确定所涉及的认知过程。第三个具体目标是确定青少年尼古丁暴露是否会导致整体或更具体的认知缺陷。第四个具体目标是确定青少年尼古丁暴露对成人认知过程的影响是短暂的还是持久的。第五个具体目的是确定尼古丁暴露对认知的影响是由青少年暴露模型观察到的，反映的是发育中的一个敏感时期，还是成年期尼古丁暴露也可能引起的损害。第六个具体目标是检查青春期尼古丁暴露对雄性和雌性大鼠认知过程影响的潜在性别差异的证据。拟议的研究将描述青春期尼古丁对成年大鼠认知过程的影响的性质，这些影响的程度和持久性，它们是否反映了发育的敏感时期，以及青春期尼古丁暴露对成年认知的影响是否存在相关的性别差异。研究结果将为进一步探索青少年尼古丁暴露对成人认知能力影响的神经基础奠定基础。公共卫生相关性：拟议的研究将描述青春期尼古丁对成年大鼠认知过程的影响的性质，这些影响的程度和持久性，它们是否反映了发育的敏感时期，以及青春期尼古丁暴露对成年认知的影响是否存在相关的性别差异。研究结果将为进一步探索青少年尼古丁暴露对成人认知能力影响的神经基础奠定基础。研究结果还将提供有关青少年尼古丁暴露在多大程度上对成人认知能力构成威胁这一重要公共卫生问题的新信息。

DESCRIPTION (provided by applicant): Recent research has shown that adolescent drug exposure can cause long-lasting changes in brain physiology, brain reward systems, susceptibility to later addiction, and simple behavior. The research proposed in this application involves a serial pattern learning paradigm for studying rat complex cognitive processes that is tightly modeled after nonverbal paradigms for studying high-level cognitive functions in humans. This serial pattern learning method has demonstrated that adolescent nicotine exposure causes cognitive dysfunction in adult rats. We propose to continue this line of research to investigate the magnitude and nature of the cognitive deficits produced by adolescent exposure to nicotine using this model system for studying the function and dysfunction of cognitive and neural systems involved in complex cognitive processes in rats. The proposed studies will use the serial pattern learning paradigm to achieve several specific aims to achieve the general goal of the research: The first specific aim is to conduct a dose-response study with established parameters from the preliminary study to investigate the dose-response effects of adolescent nicotine exposure on adult cognitive processes. The second specific aim is to characterize the nature of the effects on adult cognitive processes produced by adolescent nicotine exposure and to identify the cognitive processes involved. The third specific aim is to determine whether adolescent nicotine exposure produces global or more specific cognitive deficits. The fourth specific aim is to determine whether adolescent nicotine exposure effects on adult cognitive processes are transient or long-lasting. The fifth specific aim is to determine whether nicotine exposure effects on cognition observed with the adolescent exposure model reflect a sensitive period in development or an impairment that can also be induced by nicotine exposure in adulthood. The sixth specific aim is to examine evidence for potential sex differences in effects of adolescent nicotine exposure on cognitive processes in male and female rats. The proposed research will characterize the nature of adolescent nicotine effects on adult rat cognitive processes, the magnitude and persistence of these effects, whether or not they reflect a sensitive period in development, and whether there are associated sex differences in adult cognitive effects of adolescent nicotine exposure. The results will lay the groundwork for future studies to explore the neural basis of adolescent nicotine exposure effects on adult cognitive capacity. PUBLIC HEALTH RELEVANCE: The proposed research will characterize the nature of adolescent nicotine effects on adult rat cognitive processes, the magnitude and persistence of these effects, whether or not they reflect a sensitive period in development, and whether there are associated sex differences in adult cognitive effects of adolescent nicotine exposure. The results will lay the groundwork for future studies to explore the neural basis of adolescent nicotine exposure effects on adult cognitive capacity. The results will also provide new information regarding the important public health question of the extent to which adolescent nicotine exposure is a threat to adult cognitive capacity.