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

重复剥夺提示诱导的酒精寻求的神经元基础

• 批准号: 8524073
• 负责人: WILLIAM J MCBRIDE
• 金额: $ 31.2万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-10 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8524073
• 关键词: Abstinence; Alcohol consumption; Alcohols; Behavior; Brain; Cues; Dopamine; Drug Metabolic Detoxication; Ethanol; Event; Experimental Designs; Feedback; Foundations; GABA Receptor; Glutamate Receptor; Glutamates; Goals; Knowledge; Life; Limbic System; Measures; Mediation; Microdialysis; Microinjections; Neurons; Odors; Pathway interactions; Procedures; Rattus; Recovery; Regulation; Relapse; Rewards; Self Administration; System; Techniques; Testing; alcohol seeking behavior; behavior change; craving; deprivation; drinking; gamma-Aminobutyric Acid; in vivo; mesolimbic system; neural circuit; neuromechanism; neuronal circuitry; neurotransmission; novel; prevent; problem drinker; public health relevance; receptor; treatment strategy

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.

描述（由申请人提供）：酗酒者会经过多种排毒，每一集都更加严重，并且每发情节的复发可能性更高。此外，与饮酒相关的提示可以增强“渴望”并沉淀复发。该项目的总体目标是确定提示诱导的乙醇（ETOH）寻求行为的神经元机制，以及重复剥夺周期对这些机制具有的影响。总体假设是，在中索素 - 纤维膜系统中，多巴胺（DA）和谷氨酸（GLU）途径的活性增加了，这是提示提示引起的寻求EtOH的行为以及这些途径的活性，而这些途径的活性通过反复的剥夺周期进一步增强。帕夫洛维亚自发恢复（PSR）测试将用于测量延长禁欲后酒精饮食（P）大鼠中寻求eTOH的行为的表达。反复的2周禁欲和操作乙醇的循环将用于评估反复剥夺对提示引起的ETOH寻求eTOH行为的影响。非网络升华（NNF）和常规体内微透析技术将用于检查DA，GLU和GABA系统参与ETOH寻求ETOH的行为，以及这些系统与不同的提示和反复剥夺相关的系统的变化。微注射程序将用于识别与寻求EtOH寻求行为有关的途径和受体。 AIM 1将确定气味线索的相互作用，并反复剥夺寻求Etoh的行为和发射器释放。 AIM 2将评估反复剥夺对中膜系统中DA，GLU和GABA基底神经递质的影响，该系统在没有ETOH的情况下一直存在。 AIM 3将使用显微注射技术来评估不同受体在调节提示引起的寻求EtOH的行为中的参与。总体而言，该项目将提供有关调节提示引起的寻求ETOH的行为以及反复剥夺对这些神经元系统的影响的重要信息。