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

描述(申请人提供)：酗酒者经历多次戒毒，每一次发作都更加严重，复发的可能性也随着每一次发作而增加。此外，与饮酒有关的暗示可能会增强“渴望”，并促使再次饮酒。这个项目的总体目标是确定线索诱导的乙醇(Etoh)寻找行为的神经机制，以及重复剥夺循环对这些机制的影响。总的假设是，中脑皮质-边缘系统中多巴胺(DA)和谷氨酸(Glu)通路的活性增加是线索诱导的乙醇寻找行为的基础，这些通路的活性随着重复的剥夺循环而进一步增强。巴甫洛夫自发恢复(PSR)试验将被用来测量酒精偏好(P)大鼠在长期戒酒后的乙醇寻求行为的表达。重复两周的禁欲和可操作的酒精获取循环将被用来评估重复剥夺对线索诱导的乙醇寻求行为的影响。无净通量(NNF)和传统的体内微透析技术将被用来研究DA、Glu和GABA系统在寻找乙醇行为中的参与，以及这些系统与不同的线索和重复的剥夺相关的变化。微量注射程序将被用来识别参与调节乙醇寻求行为的途径和受体。目的1确定气味线索和重复剥夺对乙醇寻找行为表达和递质释放的交互作用。目的2将评估反复剥夺对中-边缘系统中DA、Glu和GABA基础神经传递的影响，在没有乙醇的情况下持续存在。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乙醇寻找行为中的作用。总体而言，该项目将提供有关调节线索诱导的乙醇寻找行为的神经机制以及反复剥夺对这些神经系统的影响的重要信息。

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.