Neuronal underpinnings of repeated deprivations on cue-induced alcohol-seeking

描述（由申请人提供）：酗酒者经历多次戒毒，每一次都更严重，每一次复发的可能性更高。此外，与饮酒有关的线索会增强“渴望”，并促使饮酒复发。该项目的总体目标是确定线索诱导乙醇（EtOH）寻求行为的神经元机制，以及反复剥夺周期对这些机制的影响。总的假设是，中皮层边缘系统中多巴胺（DA）和谷氨酸（Glu）通路活性的增加是线索诱导的ettoh寻求行为的基础，这些通路的活性在反复的剥夺循环中进一步增强。巴甫洛夫自发恢复（PSR）测试将用于测量酒精偏好(P)大鼠在长期戒酒后寻求etoh行为的表达。重复的2周禁欲周期和可操作的乙醇获取将被用来评估反复剥夺对线索诱导的etoh寻求行为的影响。无净通量（NNF）和传统的体内微透析技术将用于检查DA、Glu和GABA系统在寻求etoh行为中的作用，以及这些系统在不同线索和反复剥夺相关的变化。显微注射程序将用于识别参与调节etoh寻求行为的途径和受体。目的1将确定气味线索和反复剥夺对etoh寻求行为表达和递质释放的相互作用。目的2将评估反复剥夺对中边缘系统中持续存在的DA、Glu和GABA的基础神经传递的影响。目的3将使用显微注射技术来评估不同受体在调节线索诱导的etoh寻求行为中的作用。总的来说，该项目将提供重要的信息，涉及调节线索诱导的etoh寻求行为的神经元机制，以及反复剥夺对这些神经元系统的影响。

DESCRIPTION (provided by applicant): Alcoholics go through multiple detoxifications with each episode being more severe and the likelihood of relapse higher with each episode. In addition, cues associated with alcohol drinking can enhance 'craving' and precipitate relapse drinking. The overall goals of this project are to determine neuronal mechanisms underlying cue-induced ethanol (EtOH)-seeking behavior and the effects that repeated deprivation cycles have on these mechanisms. The overall hypothesis is that increased activities of dopamine (DA) and glutamate (Glu) pathways within the meso-cortico-limbic system underlie cue-induced EtOH-seeking behavior and the activities of these pathways are further enhanced with repeated deprivation cycles. A Pavlovian Spontaneous Recovery (PSR) test will be used to measure expression of EtOH-seeking behavior in alcohol-preferring (P) rats following prolonged abstinence. Repeated 2-week cycles of abstinence and operant ethanol access will be used to evaluate the effects of repeated deprivations on cue-induced EtOH-seeking behavior. No-net-flux (NNF) and conventional in vivo microdialysis techniques will be used to examine the involvement of DA, Glu and GABA systems in EtOH-seeking behavior, and changes in these systems associated with distinct cues and repeated deprivations. Microinjection procedures will be used to identify pathways and receptors involved in regulating EtOH-seeking behavior. Aim 1 will determine the interactions of odor cues and repeated deprivations on expression of EtOH-seeking behavior and transmitter release. Aim 2 will assess the effects of repeated deprivations on basal neurotransmission of DA, Glu and GABA within the meso-limbic system that persists in the absence of EtOH. Aim 3 will use microinjection techniques to assess the involvement of different receptors in regulating cue-induced EtOH-seeking behavior. Overall, this project will provide important information on neuronal mechanisms involved in regulating cue-induced EtOH-seeking behavior and the impact of repeated deprivations on these neuronal systems.