Gene expression associated with the CNS reinforcing act*

这个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电路，这可能与过量饮酒有关，并导致酒精复发。在这项提议中要检验的总体假设是，反复向VTA自我注射乙醇会导致扩展的杏仁核主要组成部分的基因表达发生变化。以往的研究和初步数据表明，VTA在调节强化过程中起着关键作用，与前VTA相比，VTA后部可能有不同的神经元系统支持强化过程，而VTA后部支持E强化。这项建议的目的是描述扩展杏仁核内神经元变化的特征，这是E自身注射到VTA后部的结果。本研究的具体目的1是通过对近交系酒精成瘾(IP)大鼠在完成8次自我给药后2小时和6小时，在VTA后部向脑内注入150 mg%E，观察其对伏隔核壳核(ACB-sh)、杏仁中央核(CEA)和内侧前额叶皮质(MPFC)基因表达的影响。具体目的2将确定后VTA内注入150 mg%E的ICSA对酒精嗜好(P)大鼠(A)在两次消退后和(B)在酒精自我滴注恢复后对ACb-sh、CEA和mPFC基因表达的影响。特定目标3将确认利用原位杂交和实时聚合酶链式反应技术通过微芯片阵列程序获得的特定目标1和2中观察到的关键结果。拟议项目的结果将提供有关杏仁核内神经系统和受体的有价值的信息，这些系统和受体参与调节酒精的奖赏特性。

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.