The Effect of Glutamatergic Modulation on Cocaine Self-Administration

谷氨酸能调节对可卡因自我给药的影响

• 批准号: 8656675
• 负责人: Elias Dakwar
• 金额: $ 19.38万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-05-01 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8656675
• 关键词: Abstinence; Affinity; Anesthetics; Anterior; Antidepressive Agents; Attention; Behavior; Cocaine; Cocaine Dependence; Cocaine Users; Consent; Crack Cocaine; Cross-Over Studies; Cues; Data; Depression and Suicide; Development; Disease; Disease remission; Dissociation; Dose; Double-Blind Method; Drug Metabolic Detoxication; Drug usage; Ecology; Equilibrium; Exploratory/Developmental Grant; Functional disorder; Genetic Crossing Over; Glutamates; Goals; Hour; Human; Impulsivity; Individual; Infusion procedures; Inpatients; Intervention; Interview; Investigation; Ketamine; Laboratories; Lorazepam; Measures; Methods; Midazolam; Monitor; Motivation; N-Methyl-D-Aspartate Receptors; National Institute of Mental Health; Neuronal Plasticity; Outcome; Outpatients; Participant; Pattern; Pharmaceutical Preparations; Phase; Play; Population; Procedures; Protocols documentation; Psychotic Disorders; Public Health; Randomized; Randomized Controlled Trials; Refractory; Relapse; Research; Research Personnel; Rhode Island; Risk; Role; Saline; Self Administration; Self Efficacy; Stress; System; Testing; Therapeutic Effect; Toxicology; Urine; Visual; active control; analog; cingulate cortex; clinically relevant; cocaine use; craving; drug abuser; drug development; follow-up; innovation; mindfulness; public health relevance; treatment strategy; volunteer

DESCRIPTION (provided by applicant): Disruptions in the glutamatergic system represent an innovative target of medications development for cocaine dependence. Our preliminary investigations with ketamine, a glutamatergic modulator with potent prefrontal effects, suggest that it represents a promising Candidate. Alongside being safely administered, with no development of psychosis or ketamine misuse, we found that sub-anesthetic ketamine led to significant changes in measures of motivation to stop cocaine use, when compared to an active control (n=8). Further, ketamine had promising effects on cue-induced craving. This project aims to examine whether these promising effects extend to cocaine self- administration. We will evaluate the effect of a single sub-anesthetic dose of ketamine (0.11 mg/kg over 2 minutes, followed by 0.60 mg/kg over 50 minutes) on cocaine self- administration in 20 non-treatment seeking non-depressed cocaine-dependent individuals who complete a 9-week combined laboratory-inpatient and outpatient double- blind, cross-over, randomized, controlled study. Participants will be provided a choice session of five cocaine choices 24 hours following each active infusion. We predict that, compared to midazolam, ketamine will significantly reduce the number of cocaine choices during the choice session. Secondary aims pertain to the effect of ketamine on cocaine-related deficits that implicate prefrontal dysfunction, such as stress sensitivity, craving, impulsivity, low motivation, low self-efficacy, and low mindfulness. Thus, we aim to evaluate a highly innovative intervention in a manner that has the capacity to make important and unprecedented contributions to the field. An effect of ketamine on cocaine self-administration would suggest that brief potent glutamatergic modulation represents a possible treatment strategy for cocaine dependence that merits further investigation.

描述（由申请人提供）：谷氨酸能系统中的破坏代表了可卡因依赖性药物开发的创新目标。我们对具有有效前额叶作用的谷氨酸能调节剂氯胺酮进行的初步研究表明，它代表了有前途的候选人。除了没有精神病或氯胺酮滥用的发展外，我们发现亚手提氯氨酸与主动对照相比，次动感氯胺酮导致停止可卡因使用的动机措施的重大变化（n = 8）。此外，氯胺酮对提示引起的渴望具有有希望的影响。该项目旨在检查这些有希望的影响是否扩展到可卡因自我给药。我们将评估单个亚您的氯胺酮（在2分钟内0.11 mg/kg，0.11 mg/kg，然后在50分钟内为0.60 mg/kg）评估可卡因自我给药的20种非治疗中的可卡因自我给药，从而寻求非抑郁的可卡因可卡因依赖性个体，这些个人完成了9周的9周组合实验室构成的实验室且随机构成的型号，并进行了外观型型型盲型和交叉，并进行了交叉，并构成了交叉，并构成。每次活跃输液后24小时，将为参与者提供五个可卡因选择的选择。我们预测，与咪达唑仑相比，氯胺酮在选择会议期间将大大减少可卡因选择的数量。次要目的与氯胺酮对可卡因相关的缺陷的影响有关，这些缺陷暗示前额叶功能障碍，例如压力敏感性，渴望，冲动性，低动力，自我效能低下，自我效能低下和正念较低。因此，我们 旨在以有能力为该领域做出重要和前所未有的贡献的方式评估高度创新的干预措施。氯胺酮对可卡因自我给药的影响表明，短暂的有效谷氨酸能调节是可卡因依赖性的可能治疗策略，值得进一步研究。