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: 8876507
• 负责人: DAVID A. KAREKEN
• 金额: $ 56.9万
• 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/8876507
• 关键词: Adolescent; Adult; Affect; Affinity; Age; Alcohol consumption; Alcoholic Intoxication; Alcoholism; Alcohols; Alleles; Animal Model; Animals; Brain; Cerebrum; Characteristics; Corpus striatum structure; Cues; Data; Drug usage; Family; Family history of; Functional Magnetic Resonance Imaging; Genetic; Genotype; Goals; Health; Heavy Drinking; Homozygote; Human; Individual; Inherited; Intoxication; Intravenous; Laboratories; Lead; Learning; Link; Measures; Medial; Mediating; 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; Solutions; Stimulus; Sucrose; Syndrome; System; Techniques; Testing; Ventral Striatum; Youth; addiction; alcohol cue; alcohol effect; alcohol exposure; alcohol related problem; alcohol use disorder; drinking; endogenous opioids; improved; in vivo imaging; insight; interest; preference; problem drinker; reinforcer; response; 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 �-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 �-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。我们的目标是确定是否饮酒和家庭 酗酒与大脑对强烈甜味的联想感觉反应有关，这是一种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或在道德上被禁止饮酒的人（例如戒酒者）进行检查。我们的中心假设是，后眶皮层对强烈甜味的联想感觉（BOLD fMRI）反应与滥用饮酒、自我饮酒有关 （在实验室测量）和家族酗酒。目标 1：测试酗酒和酒精相关问题是否与后眶额叶对高甜味觉刺激的反应程度有关。假设 1：(a) 酗酒者对高甜度蔗糖溶液的眶额反应比社交场合饮酒者更大； (b) 与酒精相关的问题与眶额反应呈正相关。目标 2：确定自我饮酒是否与甜味反应的强度有关。假设 2：眼眶对口服蔗糖的反应程度与经过验证的静脉自我注射酒精实验室范例中达到的首选酒精中毒水平呈正相关。目标 3：确定酗酒家族史是否与酗酒程度有关 对甜味的反应。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) 金钱奖励的反应之间的关联。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（内侧前额叶）引起的反应相关。假设4b：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α-阿片受体基因型与奖励系统对甜味味觉刺激的反应之间的关联。内源性阿片类药物介导对蔗糖和酒精的中枢反应。假设 5：α-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 确定内表型酒精中毒风险的生理特征的目标，并将验证针对许多人群的调查，无论年龄或饮酒史如何。通过这种方式，我们可以获得对导致酗酒的大脑风险途径的新见解。