Chronic Drinking Effects on Cocaine Self-Administration

长期饮酒对可卡因自我给药的影响

• 批准号: 7279148
• 负责人: SCOTT M OSTER
• 金额: $ 2.88万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7279148
• 关键词: Acute; Affect; Alcohol abuse; Alcohol consumption; Alcohols; Amygdaloid structure; Animals; Area; Behavior; Brain; Brain region; Cannabinoids; Chronic; Cocaine; Cocaine Users; Condition; Dependence; Development; Discrimination; Dopamine; Dose; Drug abuse; Ethanol; Exposure to; Fellowship; Goals; Hippocampus (Brain); Human; Illicit Drugs; Individual; Infusion procedures; Knowledge; Lead; Learning; Legal; Measures; Medial; Mediating; Methods; Microdialysis; Microinjections; Names; Neuraxis; Neurotransmitters; Nucleus Accumbens; Numbers; Opiates; Pathway interactions; Pharmaceutical Preparations; Pharmacologic Substance; Prefrontal Cortex; Property; Psychological reinforcement; Purpose; Range; Rattus; Research; Research Proposals; Rewards; Self Administration; Self-Administered; Site; Substance abuse problem; System; Techniques; Ventral Tegmental Area; addiction; chronic alcohol ingestion; drinking; drug of abuse; executive function; expectation; extracellular; innovation; mesolimbic system; neuroadaptation; neurochemistry; neurotransmission; novel; psychostimulant; reinforcer; relating to nervous system; response; therapy development; transmission process

DESCRIPTION (provided by applicant): The ultimate goal of this proposal is to investigate the degree to which chronic exposure to one drug of abuse (e.g. alcohol) may increase the propensity to self-administer another distinct type of drug (e.g. cocaine). The mesolimbic dopamine (DA) system appears to regulate, in part, the acute reinforcing properties of both ethanol (EtOH) and cocaine. The hypothesis of the present proposal is that chronic EtOH drinking enhances the reinforcing properties of cocaine as a result of neuroadaptations in the mesolimbic DA pathway. The intracranial self-administration (ICSA) technique has been used to reliably identify specific brain regions involved in the initiation of response-contingent behaviors associated with the delivery of a reinforcer. Thus, ICSA will be used to evaluate the reinforcing properties of cocaine in specific limbic brain areas. In addition, the microinjection-microdialysis paradigm has been successfully used to quantify neurochemical responses to the application of drugs of abuse to discrete brain regions. This technique will be used to measure DA-ergic response in the nucleus accumbens (Acb) following acute cocaine administration into the ventral tegmental area (VTA). The overall purpose of this study is to establish whether or not chronic EtOH drinking increases the sensitivity of the mesolimbic DA pathway to the reinforcing effects of cocaine in P rats, and if this increased sensitivity involves changes in DA transmission.

描述（由申请人提供）：该提案的最终目标是调查长期暴露于一种滥用药物（例如酒精）的程度，可能会增加自我管理另一种不同类型的药物（例如可卡因）的倾向。中唇多巴胺（DA）系统似乎部分调节乙醇（ETOH）和可卡因的急性增强特性。本提案的假设是，由于中唇型DA途径的神经适应性，慢性ETOH饮酒增强了可卡因的增强特性。颅内自我管理（ICSA）技术已被用来可靠地确定与加强剂提供相关的响应抗反应行为涉及的特定大脑区域。因此，ICSA将用于评估可卡因在特定边缘大脑区域中可卡因的增强特性。此外，已成功使用微注射微透析范式来量化对滥用药物在离散大脑区域中应用的神经化学反应。该技术将用于测量急性可卡因施用进入腹侧段区域（VTA）后，伏隔核（ACB）中的DA抗反应。这项研究的总体目的是确定慢性EtOH饮酒是否会增加中唇型DA途径对可卡因在P大鼠中增强作用的敏感性，并且如果这种提高的敏感性涉及DA传播的变化。