ETHANOL NICOTINE INTERACTION IN ALCOHOL PREFERRING RATS

这份申请是关于资助一家探索性国际公司 合作研究遗传和神经生物学基础 酗酒行为的证据。合作网站是印第安纳州 美国印第安纳波利斯大学酒精研究中心 和加拿大多伦多的成瘾研究基金会(ARF)。 这两家公司都建立了酒精研究人员，他们将带来独特的 为这一协作努力提供资源和专业知识。独一无二的 ARF为该项目带来的资源是选择性培育的酒精- 更喜欢HARF和不喜欢IARF大鼠品系 基于有限准入饮酒范例开发，以模仿 酗酒。IARC为该项目带来的独特资源是 高酒精偏好和低酒精偏好LAD大鼠 线路，在24小时的基础上选择，自由选择(连续接入) 消耗10%的乙醇。重要的是，这两对被选中的 品系来源于相同的异种品系N/NIH大鼠。这个 因此，协作代表着前所未有的机会 比较和对比行为和神经生物学特征 与两种不同选择的饮酒表型有关， 作为揭示潜在共同机制的一种方式。发起 在这次合作中，我们将解决酒精这个重要问题- 尼古丁相互作用并将实验室带到协作中 威廉·科里格尔的资源和专业知识，研究的先驱 实验动物的尼古丁自我给药。我们建议 研究是否存在线差异在：L)的急性影响 尼古丁和乙醇对自发性活动和身体的影响 温度；2)对尼古丁作用的敏化发展 和乙醇对重复尼古丁或酒精后的运动活动的影响 酒精注射；3)急性和慢性尼古丁的影响 酒精消费的前处理；4)获得的速度 以及静脉注射尼古丁的程度。

This application regards funding of an exploratory international collaboration to study the genetic and neurobiological underpinnings of alcohol-seeking behavior. The collaborating sites are the Indiana University Alcohol Research Center (IARC) in Indianapolis, USA, and the Addiction Research Foundation (ARF) in Toronto, Canada. Both have established alcohol researchers who will bring unique resources and expertise to this collaborative effort. The unique resource ARF brings to the project are the selectively-bred alcohol- preferring HARF and nonpreferring IARF rat lines that are being developed, based on the limited-access drinking paradigm to mimic binge drinking. The unique resource IARC brings to the project are the high alcohol-preferring HAD and low alcohol-preferring LAD rat lines, selected on the basis of 24 h. free-choice (continuous access) consumption of 10% ethanol. Importantly, both pairs of selected lines originate from the same heterogeneous stock N/Nih rat. The collaboration, therefore, represents an unprecedented opportunity to compare and contrast the behavioral and neurobiological traits that are associated with the two differently selected drinking phenotypes, as a way of uncovering potentially common mechanisms. To initiate the collaboration, we will address the important question of alcohol- nicotine interaction and bring to the collaboration the laboratory resources and expertise of William Corrigall, a pioneer in studying nicotine self-administration by the laboratory animal. We propose studies to examine if line differences exist in: l) the acute effects of nicotine and ethanol on spontaneous locomotor activity and body temperature; 2) development of sensitization to the effects of nicotine and ethanol on locomotor activity following repeated nicotine or ethanol administration; 3) the effects of acute and chronic nicotine pretreatment on alcohol consumption; and 4) the rate of acquisition and extent of IV nicotine self-administration.