Electrophysiological ensembles organization during alcohol cue-induced intake and

酒精提示诱导摄入和摄入期间的电生理集合组织

• 批准号: 8592506
• 负责人: David Nathaniel Linsenbardt
• 金额: $ 4.79万
• 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: 2013-08-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8592506
• 关键词: Abstinence; Address; Alcohol consumption; Alcoholism; Alcohols; Animal Model; Animals; Architecture; Area; Behavior; Behavioral; Biological Neural Networks; Brain; Brain region; Cells; Coupled; Cues; Data; Diagnosis; Exhibits; Extinction (Psychology); Genetic; Genetic Predisposition to Disease; Genetic Risk; Goals; Heavy Drinking; Human; Image; Indiana; Individual; Intake; Intoxication; Lead; Maintenance; Maps; Measures; Mediating; Methods; Mission; Mus; National Institute on Alcohol Abuse and Alcoholism; Neurobiology; Neurons; Pattern; Population; Population Dynamics; Predisposition; Prefrontal Cortex; Process; Rattus; Recording of previous events; Relapse; Relative (related person); Resistance; Resolution; Rewards; Risk; Rodent; Role; Smell Perception; Staging; Stimulus; System; Taste Perception; Techniques; Time; Vision; Vulnerable Populations; Wistar Rats; Work; addiction; alcohol abstinence; alcohol availability; alcohol craving; alcohol cue; alcohol effect; alcohol relapse; alcohol seeking behavior; alcohol use disorder; awake; binge drinking; craving; drinking; effective therapy; interest; neuroimaging; neuromechanism; neurophysiology; novel; prevent; problem drinker; public health relevance; relating to nervous system; research study; response; treatment strategy

DESCRIPTION (provided by applicant): Environmental stimuli such as the taste, smell, and sight, of a favorite alcoholic drink can become salient cues that increase craving for alcohol and lead individuals to continue to drink to the point of intoxication (or well beyond). These same cues can also cause craving and relapse in individuals who have abstained from alcohol for long periods of time. Because continued excessive alcohol intake and relapse following abstinence are both hallmarks of alcoholism, understanding the brain regions and processes that regulate cue-evoked alcohol seeking are critical to develop effective treatment strategies for these alcoholic individuals. Interestingly, neural activity within an area of the brain known as th prefrontal cortex (PFC) is now known to be critically involved in regulating how alcohol associated cues elicit craving, alcohol seeking, and intake. However, the exact changes in neural activity that mediate continued excessive alcohol intake and/or craving and relapse are poorly understood. We also have only a very limited understanding of how populations with genetic risk for developing alcoholism might exhibit abnormal neural processing regimes in the PFC, which make them more vulnerable to cue-related craving. We hypothesize that neural networks in the PFC will be more robustly effected by alcohol-paired cues in vulnerable populations than non-vulnerable. We also hypothesize that PFC neuronal networks are more resistant to re-mapping in genetically vulnerable populations during periods of abstinence from alcohol. These abnormal neuronal network processes might contribute to heightened cue-evoked craving and drive both continued excessive alcohol intake, as well as relapse following periods of abstinence. Our broad, long-term objective is to develop a comprehensive understanding of how neuronal networks (ensembles) within the PFC are altered by alcohol associated cues. We will accomplish this by using state-of-the-art electrophysiological recording and analysis techniques of large populations of cells in the awake behaving rodent to determine, for the first time, how instantaneous shifts in PFC ensemble activity evoked by alcohol paired cues: 1) contribute to the maintenance of binge- drinking and are modified during extinction, and 2) initiate relapse-like behavior. We will evaluate these effects in a rat population genetically predisposed to excessive alcohol consumption (Indiana alcohol preferring P rats) and in a rat population with average genetic susceptibility to excessive alcohol consumption (Wistar rats). Determining the neurobiological/neurophysiological causes and consequences of excessive alcohol consumption as well as the role of genetic vulnerability to excessive alcohol intake are directly relevant to the mission of the NIAAA. Specifically, the proposed studies will reveal the neurobiological origins of why genetically vulnerable populations respond to alcohol, and alcohol-paired cues, differently. This will lead us to a better understanding of why and how alcohol can cause addiction and will help us develop strategies to prevent and treat excessive drinking.

描述（由申请人提供）：最喜欢的酒精饮料的味道、气味和视觉等环境刺激可能成为显着的线索，增加对酒精的渴望，并导致个人继续饮酒直至中毒（或远远超过）。这些相同的暗示也会导致长期戒酒的人对酒精的渴望和复发。由于持续过量饮酒和戒酒后复发都是酗酒的标志，因此了解调节提示诱发的酒精寻求的大脑区域和过程对于制定有效的治疗策略至关重要。 这些酗酒者。有趣的是，现在已知大脑前额皮质（PFC）区域内的神经活动在调节与酒精相关的线索如何引发渴望、寻求酒精和摄入方面发挥着关键作用。然而，人们对介导持续过量饮酒和/或渴望和复发的神经活动的确切变化知之甚少。对于具有酗酒遗传风险的人群如何在前额皮质中表现出异常的神经处理机制，我们的了解也非常有限，这使得他们更容易受到与线索相关的渴望的影响。我们假设，与非弱势群体相比，弱势群体中前额皮质的神经网络更容易受到酒精配对线索的影响。我们还假设，基因脆弱人群在戒酒期间，PFC 神经元网络对重新映射的抵抗力更强。这些异常的神经元网络过程可能会加剧提示诱发的渴望，并导致持续过量饮酒，以及戒酒后复发。我们广泛、长期的目标是全面了解前额皮层内的神经元网络（整体）如何被酒精相关线索改变。我们将通过使用最先进的电生理学记录和分析技术，对清醒行为啮齿动物的大量细胞进行分析，首次确定酒精配对线索引起的 PFC 整体活动的瞬时变化是如何实现的：1）有助于维持酗酒并在灭绝过程中发生改变，2）引发类似复发的行为。我们将在遗传上易过度饮酒的大鼠群体（印第安纳州酒精偏好 P 大鼠）和对过度饮酒具有平均遗传易感性的大鼠群体（Wistar 大鼠）中评估这些影响。确定过量饮酒的神经生物学/神经生理学原因和后果以及遗传易感性对过量饮酒的影响与 NIAAA 的使命直接相关。具体来说，拟议的研究将揭示为什么遗传上易受影响的人群对酒精和酒精配对线索的反应不同的神经生物学起源。这将使我们更好地理解酒精为何以及如何导致成瘾，并帮助我们制定预防和治疗过度饮酒的策略。