Brain reward responses to sweet tastes in alcoholism risk

酒精中毒风险中大脑对甜味的奖励反应

基本信息

批准号：
9258372
负责人：
DAVID A. KAREKEN
金额：
$ 59.55万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-06-20 至 2019-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9258372
关键词：
Adolescent Adult Affect Affinity Age Alcohol consumption Alcoholic Intoxication Alcoholism Alcohols Alleles Animal Model Animals Awareness Brain Cerebrum Characteristics Corpus striatum structure Cues Data Drug usage Ethics Family Family history of Functional Magnetic Resonance Imaging Genetic Genotype Goals Heavy Drinking Homozygote Human Individual Inherited Intoxication Intravenous Laboratories Lead Learning Legal Link Measures Medial Mediating National Institute on Alcohol Abuse and Alcoholism Nature Opioid Receptor Oral Pathway interactions Pattern Phenotype Physiological Population Prevention Property Receptor Gene Recording of previous events Research Rewards Risk Risk Factors Self Administration Sensory Stimulus Sucrose Syndrome System Taste Perception Techniques Testing Ventral Striatum Youth addiction alcohol cue alcohol effect alcohol exposure alcohol measurement alcohol related problem alcohol use disorder drinking endogenous opioids improved in vivo imaging insight interest preference problem drinker public health relevance reinforcer response reward anticipation social sweet taste perception trait

项目摘要

DESCRIPTION (provided by applicant): A critical need remains to identify how the brain's reward system is altered by alcoholism risk. Our objective is to determine if drinking and familial alcoholism are related to the brain's associative sensory response to an intensely sweet taste- a primary reward repeatedly linked to animal and human drug use. The rationale for the approach is to allow examination of those who have yet to learn the relationship between alcohol cues and intoxication, or who are ethically precluded from drinking (e.g., abstinent alcoholics). Our central hypothesis is that associative sensory (BOLD fMRI) responses to an intensely sweet taste in posterior orbital cortex are associated with abusive drinking, alcohol self-administration (measured in the lab), and familial alcoholism. Aim 1: Test if abusive drinking and alcohol-related problems are associated with the magnitude of the posterior orbitofrontal response to a highly sweet gustatory stimulus. Hypothesis 1: (a) Heavy drinking subjects have larger orbitofrontal responses to a highly sweet sucrose solution than subjects who drink socially; (b) alcohol-related problems correlate positively with the orbitofrontal response. Aim 2: Determine if alcohol self-administration is related to the magnitude of the sweet taste response. Hypothesis 2: The magnitude of orbital responses to oral sucrose correlates positively with the preferred level of alcohol intoxication achieved in a validated laboratory paradigm of intravenous alcohol self-administration. Aim 3: Determine if a family history of alcoholism is related to the magnitude of the response to a sweet taste. Hypothesis 3: Subjects with a family history of alcoholism have larger orbitofrontal responses to sweet taste delivery than family history negative subjects. Aim 4: Compare the associations between alcoholism risks and responses to: a) sucrose and b) monetary rewards. Hypothesis 4a: Alcoholism risks are related more to the orbital sensory response to an intensely sweet taste than to responses provoked by monetary reward anticipation (ventral striatum) or receipt (medial prefrontal). Hypothesis 4b: Alcoholism risks comprise blunted ventral striatal responses to monetary reward anticipation, elevated medial prefrontal responses to monetary receipt, and elevated orbital sensory association responses to high-concentration sucrose. Exploratory Aim 5: Test for associations between μ-opioid receptor genotype and reward system responses to a sweet gustatory stimulus. Endogenous opioids mediate central responses to both sucrose and alcohol. Hypothesis 5: 'A' (common) allele homozygotes of the μ-opioid receptor gene (rs1799971) have lower responses to oral sucrose than 'G' allele carriers. Our proposed research advances NIAAA's goal of identifying physiological traits of endophenotypic alcoholism risk, and will validate a probe for many populations, irrespective of age or drinking history. In this way, we can obtain new insights into the cerebral risk pathways that lead to alcoholism.

描述（由申请人提供）：仍然迫切需要确定酗酒风险如何改变大脑的奖励系统。我们的目标是确定饮酒和家庭关系。酒精中毒与大脑对强烈甜味的联想感觉反应有关，这是与动物和人类吸毒反复相关的主要奖励。该方法的基本原理是允许对那些尚未了解酒精暗示和中毒之间关系的人进行检查。，或道德上禁止饮酒的人（例如，戒酒者）我们的中心假设是，后眶皮层对强烈甜味的联想感觉（BOLD fMRI）反应与此相关。酗酒、自我管理酒精（在实验室测量）和家族性酗酒目标 1：测试酗酒和酒精相关问题是否与后眶额对高甜味觉刺激的反应程度有关假设 1：（a）大量饮酒的受试者有。与社交饮酒的受试者相比，对高甜蔗糖溶液的眶额反应更大；(b) 酒精相关问题与眶额反应呈正相关。目标 2：确定酒精是否存在。自我给药与甜味反应的程度有关假设 2：对口服蔗糖的眼眶反应的程度与经验证的静脉内酒精自我给药实验室范例中达到的首选酒精中毒水平呈正相关。确定酗酒家族史是否与酗酒程度有关假设 3：有酗酒家族史的受试者比没有家族史的受试者对甜味传递有更大的眶额反应。目标 4：比较酗酒风险与对 a) 蔗糖和 b 的反应之间的关联。 ) 金钱奖励假设 4a：酗酒风险更多地与眼眶对强烈甜味的感觉反应有关，而不是与金钱奖励预期（腹侧纹状体）或收据引起的反应有关。（内侧前额叶）：酗酒风险包括腹侧纹状体对金钱奖励预期的反应迟钝、内侧前额叶对金钱收据的反应升高以及对高浓度蔗糖的眼眶感觉关联反应升高。探索性目标 5：测试 μ- 之间的关联。阿片受体基因型和奖励系统对甜味味觉刺激的反应介导对蔗糖和酒精的中枢反应。图 5：μ-阿片受体基因 (rs1799971) 的“A”（常见）等位基因纯合子对口服蔗糖的反应低于“G”等位基因携带者，我们提出的研究推进了 NIAAA 识别内表型酒精中毒风险的生理特征的目标。对许多人群进行验证，无论其年龄或饮酒史如何，我们都可以获得对导致酗酒的大脑风险途径的新见解。