Alcohol-seeking behaviors and dopaminergic function

项目说明 酒精使用障碍的一个关键诊断标准是寻求和治疗的时间不成比例 获取酒精。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励线索的反应有关，而且与寻求奖励有关 行为。因此，迫切需要确定人类腹侧纹状体多巴胺是否以及如何与 寻酒行为。这项应用的目的是确定人类腹侧纹状体多巴胺 释放与寻酒行为有关。我们研究这一现象的理由是一个关键 酒精使用障碍的特征包括不成比例的行为努力，以获得获得 酒精。我们的中心假设是，为获得酒精而花费的认知和行为努力 与人类腹侧纹状体多巴胺释放有关。使用需要以目标为导向的行为才能获得的任务 获得即兴酒精，我们的具体目标是使用多巴胺能正电子进行两个实验 发射断层扫描将： 目标1：确定是否为获得酒精(寻求酒精)作出了工具性努力 行为)与人类腹侧纹状体多巴胺能释放有关。假设1a：酒精 寻找行为增加了腹侧纹状体多巴胺的释放。假设1b：饮酒时的酒精渴求-- 寻找行为与腹侧纹状体多巴胺释放呈正相关。 目的2：确定酒精线索暴露是否增强腹侧纹状体多巴胺能释放 寻酒行为。假设2a：接触到首选酒精饮料的感官提示将 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- 寻酒行为中增强的酒精渴求与腹侧纹状体呈正相关 多巴胺的释放。 探索性目标：确定酒精寻求过程中腹侧纹状体多巴胺释放是否相关 与酒精使用和滥用有关的变量。在这里，我们探索的程度是 寻找行为中腹侧纹状体多巴胺的释放与酒精的主观强化有关， 酒精使用模式(自我报告，并在静脉注射过程中观察到)，与酒精有关 问题和性格冲动。

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.