Gene expression associated with the CNS reinforcing act*

与中枢神经系统强化作用相关的基因表达*

• 批准号: 6533695
• 负责人: ZACHARY Aaron RODD
• 金额: $ 7.34万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-27 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6533695
• 关键词: alcoholic beverage consumption; alcoholism /alcohol abuse; amygdala; behavioral /social science research tag; behavioral genetics; central nervous system; cooperative study; ethanol; gene expression; in situ hybridization; laboratory rat; microarray technology; nucleus accumbens; polymerase chain reaction; prefrontal lobe /cortex; reinforcer; relapse /recurrence; self medication; tegmentum

The long-range goals of this project are to better understand the neural circuitry underlying the reinforcing actions of ethanol (E) which may be linked to excessive alcohol drinking and contribute to alcohol relapse. The overall hypothesis to be tested in this proposal is that repeated self- administration of ethanol into the VTA produces alterations in gene expression within major components of the extended amygdala. Previous studies and preliminary data indicate that the VTA plays a key role in mediating reinforcement processes, different neuronal systems may be supporting reinforcement processes in the posterior compared to the anterior VTA, and the posterior VTA supports E reinforcement. The objectives of this proposal are to characterize neuronal alterations within the extended amygdala as a result of the self-administration of E into the posterior VTA. Specific Aim 1 will determine the effects of intra-cranial self-administration (ICSA) of 150 mg % E into the posterior VTA on gene expression in the nucleus accumbens shell (ACB-sh), central nucleus of the amygdala (CeA), and medial prefrontal cortex (mPFC) of inbred alcohol-preferring (iP) rats, 2 and 6 hr after completing 8 self- administration sessions. Specific Aim 2 will determine the effects of ICSA of 150 mg% E into the posterior VTA on gene expression in the ACB-sh, CeA, and mPFC of alcohol-preferring (P) rats (a) following two sessions of extinction and (b) after reinstatement of ethanol self- infusion. Specific Aim 3 will confirm key findings observed in specific aims 1 and 2 obtained with the microchip array procedure with in situ hybridization and real time PCR techniques. The results of the proposed project will provide valuable information on neuronal systems and receptors within the extended amygdala involved in mediating the rewarding properties of alcohol.

该项目的远程目标是更好地了解乙醇（E）的加强作用的神经回路，这可能与过量的饮酒有关并导致酒精复发。在该提案中要检验的总体假设是，乙醇反复给VTA的自我给药会在扩展杏仁核的主要成分内产生基因表达的改变。先前的研究和初步数据表明，VTA在介导增强过程中起关键作用，与前VTA相比，不同的神经元系统可能支持后部的强化过程，而后VTA支持E强化。该提案的目的是表征由于E在后VTA中进行自我管理的结果，在扩展的杏仁核内进行了神经元改变。具体目标1将确定150 mg％e的颅内自我接合（ICSA）对后VTA中VTA对基因表达的影响，对伏和胞核中的基因表达，杏仁核（CEA）的中央核（CEA）和中部前叶叶质（MPFC）（MPFC）（MPFC）（MPFC）的核心（MPFC）（ipfc）的2（iP）ipfcring（iP）ipfcress（ip）ipfring and and and and and。会议。具体目标2将确定150 mg％e的ICSA对乙醇自我输液重新定位后进行了两次灭绝和（b）之后的饮酒（P）大鼠（P）大鼠（P）大鼠（P）大鼠（P）大鼠（P）大鼠（P）大鼠（P）大鼠（P）大鼠（P）大鼠（P）大鼠（P）大鼠（a）的ICSA对基因表达的影响。特定的目标3将确认在特定目的1和2中观察到的关键发现，并通过微芯片阵列程序获得了原位杂交和实时PCR技术。拟议项目的结果将提供有关涉及介导酒精奖励性能的扩展杏仁核内神经元系统和受体的有价值信息。