Disentangling the biological links between violence and alcohol use

解开暴力和酗酒之间的生物学联系

• 批准号: 10660813
• 负责人: Marco Bortolato
• 金额: $ 53.16万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2028-02-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10660813
• 关键词: Acute; Adolescence; Adverse effects; Aggressive behavior; Alcohol consumption; Alcohols; Alleles; Anger; Animal Model; Animals; Behavioral; Biological; CRF receptor type 1; Child Abuse and Neglect; Clinical; Complex; Corticotropin-Releasing Hormone; Data; Development; Dopamine; Dose; Economic Burden; Electrophysiology (science); Enzymes; Female; Genes; Genetic Carriers; Genotype; Glutamate Receptor; Human; Impairment; Individual; Life; Link; Modeling; Monoamine Oxidase A; Mus; Mutation; N-Methylaspartate; Neurons; Nucleus Accumbens; Pathologic; Pattern; Prefrontal Cortex; Prevention; Process; Receptor Activation; Recording of previous events; Recurrence; Regimen; Research; Serotonin; Shapes; Signal Transduction; Slice; Testing; Time; Variant; Violence; alcohol abuse therapy; alcohol and other drug; alcohol comorbidity; alcohol effect; alcohol misuse; alcohol prevention; alcohol reinforcement; alcohol reward; alcohol risk; antagonist; comorbidity; conditioned place preference; drug of abuse; early life exposure; early life stress; economic impact; gene environment interaction; high risk; male; mutant; neurobiological mechanism; novel therapeutics; postnatal; preference; pup; receptor function; reinforced behavior; social; socioeconomics; transmission process

PROJECT SUMMARY/ABSTRACT Alcohol misuse is often associated with pathological aggression, a recurrent pattern of disruptive and violent behavior. Despite the significant socioeconomic burden imposed by the repercussions of this comorbidity, avail- able treatments are limited and inadequate. A critical problem in treating the association of alcohol misuse and pathological aggression lies in the complex links between these two entities: on the one hand, alcohol worsens violence propensity in predisposed individuals; on the other hand, anger and aggression increase the risk of alcohol use. Disentangling the links between these conditions is critical to developing better therapies. To study these neurobiological mechanisms, we focused on the best-characterized gene × environment (G×E) interaction underlying pathological aggression and alcohol use, occurring between low-activity alleles of the MAOA gene (encoding the enzyme monoamine oxidase A) and child maltreatment. We recently developed the first animal model of this G×E interaction by subjecting a line of mice with an MAOA hypomorphic mutation to early-life stress during the first week of life. The studies proposed in this application will test the hypothesis that the interaction of low-activity MAOA variants and child maltreatment leads to alterations of the prefrontal cortex and nucleus accumbens, which predispose to a vicious cycle of increased alcohol use and aggression. The three Aims of this proposal will focus on 1) the common neurodevelopmental mechanisms of these two problems; 2) the adverse effects of alcohol drinking on aggression; and 3) the impact of anger and social reactivity on the propensity to drink alcohol. Taken together, this research will help elucidate the mechanisms of the comorbidity of alcohol misuse and pathological aggres- sion and identify new potential targets for the prevention and treatment of alcohol-associated violence.

项目总结/文摘