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.

该项目的长期目标是更好地了解乙醇（E）强化作用的神经回路，这可能与过量饮酒有关，并有助于酒精复发。在这个提议中要测试的总体假设是，重复地将乙醇自我施用到腹侧被盖区中会在延伸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，腹侧被盖区在介导强化过程中起着关键作用，与腹侧被盖区前部相比，不同的神经系统可能支持后部的强化过程，并且后部腹侧被盖区支持E强化。这项建议的目的是表征神经元的变化，在扩展杏仁核作为一个结果的自我管理E到后腹侧被盖区。具体目标1将确定在完成8次自我给药后2小时和6小时，将150 mg % E颅内自我给药（ICSA）至后VTA对近交系酒精偏好（iP）大鼠的延髓核壳（ACB-sh）、杏仁核中央核（CeA）和内侧前额叶皮质（mPFC）中基因表达的影响。具体目标2将确定150 mg% E的ICSA进入后VTA对酒精偏好（P）大鼠ACB-sh、CeA和mPFC基因表达的影响（a）在两次消退后和（B）在恢复乙醇自我输注后。特异性目标3将证实特异性目标1和2中观察到的关键发现，这些发现是通过微芯片阵列程序和原位杂交和真实的时间PCR技术获得的。该项目的结果将提供有价值的信息，神经元系统和受体内的扩展杏仁核参与调解酒精的奖励性质。