Gene expression associated with the CNS reinforcing act*

该项目的长期目标是更好地了解乙醇(E)强化作用背后的神经回路，这可能与过量饮酒和酒精复发有关。在这个提议中要测试的总体假设是，反复的自我给药乙醇进入VTA会在延长的杏仁核的主要成分中产生基因表达的改变。先前的研究和初步数据表明，VTA在介导强化过程中起关键作用，与前VTA相比，不同的神经元系统可能支持后VTA的强化过程，后VTA支持E的强化。这一建议的目的是表征在扩展杏仁核内的神经元改变，作为自我给药E进入后VTA的结果。特异性目的1将在完成8次自我给药后2和6小时，确定150 mg % E入后侧VTA颅内自我给药（ICSA）对近亲交配嗜酒（iP）大鼠伏隔核壳（ACB-sh）、杏仁核中央核（CeA）和内侧前额叶皮层（mPFC）基因表达的影响。特异性目的2将确定150mg % 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)在两次灭绝和(b)恢复乙醇自输后。特异性目标3将证实在特异性目标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、原位杂交和实时PCR技术获得的。拟议项目的结果将提供有关神经元系统和扩展杏仁核内参与调节酒精奖励特性的受体的有价值的信息。

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.