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: 8693202
• 负责人: DAVID A. KAREKEN
• 金额: $ 60.14万
• 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/8693202
• 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; 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; public health relevance; 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(由申请者提供)：一个关键的需要仍然是确定大脑的奖励系统是如何因酒精中毒风险而改变的。我们的目标是确定饮酒和家庭成员 酒精中毒与大脑对强烈甜味的联合感觉反应有关--这是一种与动物和人类药物使用反复相关的主要奖励。这种方法的基本原理是允许检查那些尚未了解酒精暗示和醉酒之间的关系的人，或者那些在道德上被禁止饮酒的人(例如，戒酒的人)。我们的中心假设是，眼眶后皮质对强烈甜味的联合感觉(BOLD FMRI)反应与酗酒、自我饮酒有关。 (在实验室测量)，以及家族性酒精中毒。目的1：测试酗酒和酒精相关问题是否与高度甜味味觉刺激的后眼眶前额反应的大小有关。假设1：(A)大量饮酒的受试者对高甜度蔗糖溶液的眼眶额叶反应比社交饮酒的受试者大；(B)与酒精相关的问题与眼眶额叶反应呈正相关。目的2：确定酒精自我给药是否与甜味反应的大小有关。假设2：眼眶对口服蔗糖反应的大小与静脉注射酒精自我给药的验证实验室范例中实现的酒精中毒的首选水平呈正相关。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无家族史的受试者对甜味递送有更大的眼眶前额反应。目标4：比较酗酒风险和对以下结果的反应之间的关系：a)蔗糖和b)金钱奖励。假设4a：酒精中毒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)或接收(额叶内侧)引起的反应有关。假设4b：酒精中毒风险包括对金钱奖励预期的迟钝腹侧纹状体反应，对货币收入的内侧前额叶反应升高，以及对高浓度蔗糖的眼眶感觉联系反应升高。探索性目标5：测试阿片受体基因与奖赏系统对甜味刺激的反应之间的关系。内源性阿片类药物介导对蔗糖和酒精的中枢反应。假设5：阿片受体基因(Rs1799971)的‘A’(常见)等位基因纯合子比‘G’等位基因携带者对口服蔗糖的反应更低。我们建议的研究推进了NIAAA确定内表型酒精中毒风险的生理特征的目标，并将验证一项适用于许多人群的探针，无论年龄或饮酒史。通过这种方式，我们可以对导致酒精中毒的大脑风险途径获得新的见解。