Pharmacogenetic manipulation of brain regions to reduce alcohol binge drinking

大脑区域的药物遗传学操作以减少酗酒

• 批准号: 8820030
• 负责人: Angela Renee Ozburn
• 金额: --
• 依托单位: PORTLAND VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-10-01 至 2019-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8820030
• 关键词: Acute; Affect; Alcohol abuse; Alcohol consumption; Alcohol dependence; Alcohol-Related Disorders; Alcoholism; Alcohols; Animal Model; Area; Behavior; Behavioral; Biological; Biological Assay; Blood alcohol level measurement; Brain; Brain region; Breeding; Candidate Disease Gene; Cells; Chronic; Clinical Trials; Clozapine; Data; Deep Brain Stimulation; Dependence; Designer Drugs; Diagnosis; Disease; Epigenetic Process; Ethanol; Family; Gene Delivery; Gene Expression; Gene Expression Profile; Genes; Genetic; Genetic Transcription; Healthcare Systems; Individual; Intake; Knowledge; Liquid substance; Measures; Mediating; Medical; Mental disorders; Methods; Morphology; Motivation; Mus; Muscarinic Acetylcholine Receptor; Neuronal Plasticity; Neurons; Nucleus Accumbens; Oxides; Pathway Analysis; Pathway interactions; Persons; Pharmacogenetics; Property; Public Health; Published Comment; RNA; Relapse; Research; Research Priority; Rewards; Signal Transduction; Stress; Substance abuse problem; Testing; Therapeutic; Time; Viral; Weight; adverse outcome; alcohol abuse therapy; alcohol behavior; alcohol craving; alcohol measurement; alcohol relapse; alcohol research; alcohol reward; alcohol use disorder; binge drinking; differential expression; disorder later incidence prevention; drinking; drinking behavior; effective therapy; insight; neuronal circuitry; novel; public health relevance; receptor; research study; response; tool; transcription factor; transcriptome sequencing

DESCRIPTION (provided by applicant): Alcohol dependence is a devastating psychiatric disorder to individuals and their families, with substantial medical and societal impact. There exists a serious public health need to identify and characterize new and more effective treatments. Chronic alcohol intake leads to long lasting changes in reward- and stress-related neuronal circuitry. The nucleus accumbens (NAc) is an integral component of this circuitry. The stability of behavioral alterations associated with chronic alcohol abuse suggests maladaptive neuroplasticity that is likely achieved through transcriptional mechanisms. Recent clinical trials have revealed that deep brain stimulation of the NAc decreases alcohol craving and relapse in alcohol dependent subjects (Vogues et al., 2012). Much is unknown about the efficacy and mechanisms underlying treatments that alter brain activity. In the proposed studies, I will use DREADDs (designer receptors exclusively activated by designer drugs) to increase or decrease neuronal activity in the nucleus accumbens and measure alcohol binge drinking (using the limited access paradigm, drinking in the dark) and relapse-like drinking (using chronic intermittent ethanol induction of dependence followed by limited access drinking) behaviors in mice selectively bred to drink intoxicating levels of alcohol in a limited access paradigm. Interestingly, preliminary data reveal that increasing NAc activity decreases binge drinking without altering alcohol reward. Since this is the first time a study such as this has been conducted, it will be essential to determine if these changes in behavior are accompanied by changes in expression of plasticity-related genes and identify DREADD/alcohol responsive gene expression networks using whole transcriptome sequencing (RNA Seq). These findings could have vast implications for alcohol research and treatment.

描述（由申请人提供）：