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

• 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
• 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

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（由应用程序提供）：仍然需要确定酒精中毒风险改变大脑奖励系统的关键需求。我们的目标是确定饮酒和家人是否 酒精中毒与大脑对本质上甜味的感觉反应有关，这是与动物和人类吸毒的反复相关的主要奖励。该方法的理由是允许检查那些尚未学习酒精提示与中毒之间关系的人，或者在道德上被排除在饮酒中（例如，戒酒）。我们的中心假设是，在后轨道皮层中对本质上甜味的缔合感官（BOLD FMRI）与滥用饮酒，酒精自给自足有关 （在实验室中测量）和家庭酗酒。 AIM 1：测试滥用饮酒和与酒精有关的问题是否与对高度甜味的味觉刺激的后眶后反应的大小有关。假设1：（a）与在社交上喝酒的受试者相比，大量饮酒对象对高度甜蔗糖的溶液具有更大的轨道额反应； （b）与酒精相关的问题与眶额反应正相关。 AIM 2：确定酒精自我给药是否与甜味反应的大小有关。假设2：对口服蔗糖的轨道反应的大小与经过验证的静脉内酒精自我服用实验室范式中获得的首选酒精中毒水平正相关。目标3：确定酒精中毒家族史是否与大小有关 假设3：具有酒精中毒家族史的受试者对甜味递送的轨道额反应比家族史负面受试者更大。目标4：将酒精中毒风险与反应之间的关联与：a）蔗糖和b）货币回报之间的关联。假设4a：酒精中毒风险与对本质上甜味的轨道感觉反应有关，而不是对货币奖励预期（腹侧纹状体）或收据引起的反应（媒体前额叶）。假设4B：酒精中毒风险包括对货币奖励预期的腹侧纹状体反应，对货币收据的培养基前额叶升高以及轨道感觉关联对高浓度蔗糖的反应升高。探索性目的5：测试μ阿片受体基因型与奖励系统对甜味性味觉刺激的响应之间的关联。内源性阿片类药物介导了对蔗糖和酒精的中心反应。假设5：μ-阿片受体基因（RS1799971）对口服蔗糖的反应低于“ G”等位基因载体的“ A”（常见）等位基因纯合子。我们提出的研究促进了NIAAA确定内生饮酒风险的生理特征的目标，并将验证许多人群的调查，而与年龄或饮酒史无关。这样，我们可以获得对导致酒精中毒的脑风险途径的新见解。