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

描述（由申请人提供）：酗酒者经历多次解毒，每次发作都更严重，每次发作复发的可能性更高。此外，与饮酒相关的线索可以增强“渴望”并加速复发饮酒。这个项目的总体目标是确定线索诱导的乙醇（EtOH）寻求行为的神经机制和重复剥夺循环对这些机制的影响。总体假设是，增加活动的多巴胺（DA）和谷氨酸（Glu）通路的中皮质边缘系统的线索诱导的乙醇寻求行为的基础和这些途径的活动进一步增强与重复的剥夺周期。巴甫洛夫自发恢复（PSR）试验将用于测量长期戒酒后偏好酒精（P）大鼠中乙醇寻求行为的表达。将使用重复的2周戒断和操作性乙醇获取周期来评价重复剥夺对线索诱导的乙醇寻求行为的影响。无净流量（NNF）和传统的体内微透析技术将被用来检查参与的DA，Glu和GABA系统的EtOH寻求行为，并在这些系统与不同的线索和重复剥夺的变化。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。目标1将确定气味线索和重复剥夺对EtOH寻求行为表达和递质释放的相互作用。目的2将评估反复剥夺对在无乙醇的情况下持续存在的中脑边缘系统内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参与调节线索诱导的EtOH寻求行为。总的来说，这个项目将提供重要的信息，神经元机制参与调节线索诱导的EtOH寻求行为和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.