Alcohol-seeking behaviors and dopaminergic function

寻酒行为和多巴胺能功能

• 批准号: 9345999
• 负责人: DAVID A. KAREKEN
• 金额: $ 55.31万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-05 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9345999
• 关键词: Alcohol abuse; Alcohol consumption; Alcoholic Intoxication; Alcohols; Alleles; Animals; Attention; Behavior; Behavioral; Bilateral; Cognitive; Consummatory Behavior; Consumption; Corpus striatum structure; Cues; Data; Development; Diagnostic; Disease; Dopamine; Elements; Exposure to; Goals; Human; Intravenous; Knowledge; Link; Literature; Opioid Receptor; Patient Self-Report; Pattern; Pharmaceutical Preparations; Phenotype; Physiological; Population; Positron-Emission Tomography; Property; Relapse; Research; Rewards; Self Administration; Self-Administered; Sensory; Smell Perception; Stimulus; System; Taste Perception; Testing; Time; Vision; Work; alcohol availability; alcohol craving; alcohol cue; alcohol misuse; alcohol reinforcement; alcohol related problem; alcohol seeking behavior; alcohol use disorder; brain dysfunction; drug reinforcement; drug seeking behavior; experimental study; motivated behavior; neurophysiology; pre-clinical; problem drinker; response; trait impulsivity

PROJECT DESCRIPTION One critical diagnostic criterion of an alcohol use disorder is the disproportionate time spent seeking and obtaining alcohol. A considerable body of preclinical data in animals now suggests that ventral striatal dopamine release is associated, not only with the response to reward cues, but also with reward seeking behaviors. This leaves a critical need to determine if and how human ventral striatal dopamine is related to alcohol-seeking behaviors. The objective of this application is to determine if human ventral striatal dopamine release is related to alcohol seeking behaviors. Our rationale for examining this phenomenon is that a key feature of alcohol use disorders involves disproportionate behavioral effort directed toward gaining access to alcohol. Our central hypothesis is that the cognitive and behavioral effort expended to gain access to alcohol is linked to human ventral striatal dopamine release. Using a task that requires goal-directed behaviors to gain access to ad lib alcohol, our specific aims are to conduct two experiments using dopaminergic positron emission tomography that will: Aim 1: Determine if instrumental efforts exerted to gain access to alcohol (alcohol seeking behaviors) are associated with human ventral striatal dopaminergic release. Hypothesis 1a: Alcohol seeking behaviors increase ventral striatal dopamine release. Hypothesis 1b: Alcohol craving during alcohol- seeking behaviors is positively correlated with ventral striatal dopamine release. Aim 2: Determine if alcohol cue exposure potentiates ventral striatal dopaminergic release during alcohol seeking behaviors. Hypothesis 2a: Exposure to the sensory cues of a preferred alcoholic drink will potentiate ventral striatal dopamine release during effortful alcohol seeking behaviors. Hypothesis 2b: Cue- potentiated alcohol craving during alcohol-seeking behaviors is positively correlated with ventral striatal dopamine release. Exploratory aim: Determine if ventral striatal dopamine release during alcohol seeking is associated with variables related to alcohol use and abuse. Here we explore the extent to which the magnitude of ventral striatal dopamine release during seeking behaviors is related to subjective reinforcement from alcohol, alcohol use patterns (self-reported, and observed during intravenous self-administration), alcohol-related problems, and trait impulsivity.

项目描述 酒精使用障碍的一个关键诊断标准是花费不成比例的时间寻求和治疗。 得到酒精。大量的动物临床前数据表明，腹侧纹状体 多巴胺的释放不仅与对奖赏线索的反应有关，而且与奖赏寻求有关 行为。这就迫切需要确定人类腹侧纹状体多巴胺是否以及如何与 酗酒行为。本申请的目的是确定人类腹侧纹状体多巴胺 释放与酒精寻求行为有关。我们研究这一现象的基本原理是， 酒精使用障碍的特征涉及不成比例的行为努力， 酒精我们的中心假设是，为了获得酒精而付出的认知和行为努力 与人类腹侧纹状体多巴胺的释放有关使用需要目标导向行为的任务来获得 我们的具体目标是进行两个实验，使用多巴胺能正电子 发射断层扫描将： 目的1：确定是否施加了工具性努力以获得酒精（酒精寻求 行为）与人腹侧纹状体多巴胺能释放有关。假设1a：酒精 寻找行为增加腹侧纹状体多巴胺的释放。假设1b：饮酒期间的酒精渴望- 寻找行为与腹侧纹状体多巴胺释放呈正相关。 目的2：确定酒精提示暴露是否增强腹侧纹状体多巴胺能释放， 酒精寻求行为假设2a：接触到一种偏好的酒精饮料的感官线索， 在努力寻求酒精的行为中增强腹侧纹状体多巴胺的释放。假设2b：线索- 酒精寻求行为中增强的酒精渴求与腹侧纹状体正相关， 多巴胺释放 探索性目的：确定酒精寻求过程中腹侧纹状体多巴胺释放是否与 与酒精使用和滥用相关的变量。在这里，我们探讨的程度， 腹侧纹状体在寻找行为期间的多巴胺释放与来自酒精的主观强化有关， 酒精使用模式（自我报告，并在静脉自我给药期间观察到），酒精相关 问题和特质冲动