权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Laboratory Models of Cocaine Self-Administration

可卡因自我给药的实验室模型

基本信息

批准号：
7474463
负责人：
Thomas Frederick Newton
金额：
$ 8.86万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-09-20 至 2009-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7474463
关键词：
Abstinence Alcohol abuse Alcohol consumption Alleles American Animals Antidepressive Agents Area Behavior Buprenorphine CPDD protocol Clinical Clinical Trials Cocaine Cocaine Abuse Cocaine Dependence Cocaine Users Comorbidity Consensus Controlled Clinical Trials Data Dependence Development Disulfiram Dopamine Dopamine Agonists Dopamine-beta-monooxygenase Drug usage Enzymes Evaluation Exhibits Genotype Gold Human Laboratories Legal Measurement Measures Medical Methadone Modeling Mood stabilizers Norepinephrine Opiate Addiction Outcome Outcome Measure Participant Patients Pharmaceutical Preparations Pharmacotherapy Placebos Plasma Population Population Distributions Predictive Value Publishing Qualifying Relative (related person)Reporting Research Research Personnel Sampling Self Administration Series Standards of Weights and Measures Toxicology Universities Urine Validation base design enzyme activity pre-clinical programs social treatment effect volunteer

项目摘要

The problem of cocaine dependence remains a major medical, social, and legal concern, with 2.3 million Americans estimated to be current users of cocaine. The outcome from medications development efforts has generally been discouraging, excepting for results recently obtained for disulfiram. A series of clinical trials have shown that disulfiram treatment was associated with reduced cocaine use, independent of co-morbid drug or alcohol use. The validation of a human laboratory model against outcomes observed in clinical trials would be a major step forward in developing even more effective treatments for cocaine dependence. This is a crucial undertaking, since there has not been good accord between animal or human laboratory model findings and results from clinical trials. Disulfiram has a variety of actions, one of which is to inhibit dopamine beta hydroxylase, the enzyme responsible for metabolizing dopamine into norepinephrine. Recently obtained data indicate that disulfiram is particularly effective in patients with a "T" allele of dopamine beta hydroxylase; the C/T genotype is associated with reduced enzyme activity compared to the C/C genotype. We therefore propose to evaluate effects of disulfiram treatment on cocaine self-administration in genetically characterized non-treatment seeking volunteers. Participants will be screened and only those with the DBH C/T genotype will be included. Effects of cocaine self-administration will be assessed using two established human laboratory models, one developed at Columbia University and the other developed at Johns Hopkins. Based on the observed effects of disulfiram treatment in clinical trials, especially effects of disulfiram in participants with the C/T genotype, we anticipate that disulfiram treatment will decrease cocaine self-administration in the laboratory.

可卡因依赖问题仍然是一个主要的医疗、社会和法律问题，