A Human Laboratory Study to Investigate Buspirone for Cocaine Use Disorders

调查丁螺环酮治疗可卡因使用障碍的人体实验室研究

• 批准号: 8518284
• 负责人: William Walton Stoops
• 金额: $ 19.54万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8518284
• 关键词: 12 year old; Abstinence; Agonist; American; Animals; Anti-Anxiety Agents; Autoreceptors; Basic Science; Behavior Therapy; Behavioral; Buspirone; Clinical; Clinical Research; Clinical Trials; Cocaine; Cocaine Dependence; Cocaine Users; Cognitive; Data; Development; Disease; Dopamine; Dopamine Agonists; Dopamine Antagonists; Dose; Double-Blind Method; Drug usage; Health; Human; In Vitro; Intervention; Laboratories; Laboratory Research; Laboratory Study; Literature; Maintenance; Measures; Modeling; National Institute of Drug Abuse; Neuraxis; Neurosciences; Neurotransmitters; Nicotine Use Disorder; Opioid; Performance; Pharmaceutical Preparations; Pharmacodynamics; Pharmacotherapy; Physiological; Placebo Control; Placebos; Play; Public Health; Relative (related person); Reporting; Research; Role; Sample Size; Sampling; Schedule; Self Administration; Serotonin; Serotonin Receptor 5-HT1A; Stimulus; Surveys; Synapses; System; Testing; Time; Translating; Treatment Efficacy; United States; Urine; cocaine use; dopamine system; effective therapy; in vivo; meetings; novel; pre-clinical; preclinical study; receptor; reinforcer; research study; reuptake; success; tool; treatment effect

DESCRIPTION (provided by applicant): Cocaine use disorders are an unrelenting public health concern. Intensive research efforts have yielded behavioral interventions that reduce cocaine use, however, these interventions are not universally effective and treatment effects diminish over time. Development of a pharmacotherapy that enhances the efficacy of these interventions is a priority for the National Institute on Drug Abuse. In the central nervous system cocaine blocks the reuptake and induces release of dopamine and serotonin, thus a successful cocaine pharmacotherapy will likely need to target both of those neurotransmitters. Buspirone, an anxiolytic medication with limited abuse potential, is an antagonist at dopamine autoreceptors and a partial agonist at serotonin 5- HT1A receptors; both of these receptors play crucial roles in the abuse-related effects of cocaine. Dopamine autoreceptors stabilize dopaminergic tone and antagonists at these receptors can increase dopamine release. Moreover, medications with partial agonist activity have been recognized as valuable tools for managing opioid and nicotine use disorders due to their ability to stimulate receptors when neurotransmitter tone is low (i.e., during abstinence) and block receptors when neurotransmitter tone is high (i.e., following a lapse). Although buspirone produces pharmacological effects that are likely beneficial for treating cocaine dependence, we are unaware of any human laboratory research that has tested the influence of buspirone on the behavioral effects of cocaine, a notable gap in the literature considering that such research can efficiently screen potential medications prior to the conduct of large-scale clinical trials. This study will assess the reinforcing, subject- rated, cognitive, performance and physiological effects of cocaine during maintenance on buspirone. By determining how buspirone impacts the behavioral effects of cocaine, we will provide important evidence regarding the potential efficacy of this compound for managing cocaine use disorders. These results will help to broaden the current clinical neuroscience paradigm of cocaine medications development efforts beyond a focus on dopamine systems. In addition, demonstrating the initial efficacy of a commercially available drug will impact clinical research more quickly than waiting for novel molecules to be available for testing in humans.

描述（由申请人提供）：可卡因使用障碍是不懈的公共卫生问题。密集的研究工作产生了减少可卡因使用的行为干预措施，但是，这些干预措施并不普遍，并且随着时间的流逝，治疗效果会减少。发展这些干预措施的药物疗法的开发是美国国家药物滥用研究所的优先事项。在中枢神经系统中，可卡因会阻止再摄取并诱导多巴胺和5-羟色胺的释放，因此，成功的可卡因药物疗法可能需要靶向这两个神经递质。 Buspirone是一种抗滥用潜力有限的抗焦虑药，是多巴胺自身受体的拮抗剂，是5-羟色胺5- HT1A受体的部分激动剂。这两个受体在可卡因的滥用相关作用中起着至关重要的作用。多巴胺自身受体稳定多巴胺能张力和在这些受体处的拮抗剂可以增加多巴胺的释放。此外，由于在神经递质张力较低时（即在戒烟期间），神经递质张力较低时，具有部分激动剂活性的药物已被认为是管理阿片类药物和尼古丁使用障碍的有价值的工具，并且在神经递质张力较高时（即在戒烟期间）刺激受体（即，在神经递质张力较高时（即在持久）时（即，在失去后）。尽管丁螺酮会产生可能有助于治疗可卡因依赖性的药理作用，但我们不知道任何人类实验室研究都测试了丁螺酮对可卡因行为影响的影响，在文献中，考虑到此类研究可以在进行大规模临床试验之前有效筛查潜在药物的文献中的显着差距。这项研究将评估可卡因维持对丁螺酮期间可卡因的增强，受试者，认知，性能和生理影响。通过确定丁螺酮如何影响可卡因的行为影响，我们将提供有关该化合物管理可卡因使用障碍的潜在功效的重要证据。这些结果将有助于扩大可卡因药物开发工作的当前临床神经科学范式，而不是重点放在多巴胺系统上。此外，与等待新的分子可以在人类中进行测试相比，证明市售药物的初始功效会更快地影响临床研究。

项目成果

Cocaine choice procedures in animals, humans, and treatment-seekers: Can we bridge the divide?

• DOI: 10.1016/j.pbb.2015.09.020
• 发表时间: 2015-11
• 期刊: Pharmacology, biochemistry, and behavior
• 作者: Moeller SJ;Stoops WW
• 通讯作者: Stoops WW

Effects of acute buspirone administration on inhibitory control and sexual discounting in cocaine users.

急性丁螺环酮给药对可卡因使用者的抑制控制和性折扣的影响。

• DOI: 10.1002/hup.2567
• 发表时间: 2017
• 期刊: Human psychopharmacology
• 作者: Strickland,JustinC;Bolin,BLevi;Romanelli,MichaelR;Rush,CraigR;Stoops,WilliamW
• 通讯作者: Stoops,WilliamW