Mechanisms in Risk Taking: Disinhibitory Drugs of Abuse

描述（由申请人提供）：本申请旨在实现两个广泛的目标：（i）使用基于实验室行为的程序来研究滥用去抑制药物对（适应不良）人类冒险行为的影响； (ii) 确定在使用去抑制药物后表现出对冒险高度敏感的个体（特别是年轻人）的基本行为机制。 去抑制药物会导致某些行为的频率增加（否则会降低）。使用去抑制药物与许多导致有害结果的冒险行为有关，包括车祸、故意破坏、暴力犯罪、性侵犯和危险性行为。重要的是，使用去抑制药物和随之而来的危险行为在年轻人中很普遍。因此，年轻人因药物介导的冒险行为所产生的社会和行为后果是一个相当大的公共卫生问题，也是一项至关重要的科学努力。 在受控实验室条件下研究去抑制药物与冒险行为之间的关系将提供重要的科学信息。本申请中的实验旨在调查年轻人急性滥用四种药物后冒险行为的变化：酒精、大麻、苯二氮卓类药物阿普唑仑 (Xanax) 和氟硝西泮 (Rohypnol)。虽然许多年轻人使用这些药物，但并非所有人都滥用它们，也并非所有人在吸毒时都会过度冒险。因此，识别冒险行为所涉及的基本行为过程和特征可能有助于预测那些行为最有可能受到吸毒过度影响的人。 拟议的四个实验中的每一个都将采用基于实验室的任务来衡量冒险行为。这项任务已经系统地发展了几年，并且已被证明对（i）冒险的个体差异（青少年和成年人）和（ii）急性药物效应敏感。每位参与者将在急性服用上述一种去抑制药物后完成冒险任务。使用受试者内设计，将施用一系列剂量以确定剂量-效应关系。行为模式的定量分析将用于识别可能调解这种关系的因素。

DESCRIPTION (provided by applicant): This application seeks to achieve two broad objectives: (i) to study the effects of disinhibitory drugs of abuse on (maladaptive) human risk-taking using laboratory behavior-based procedures; (ii) to identify basic behavioral mechanisms operating in individuals (specifically young adults) who show heightened susceptibility to risk taking following use of disinhibitory drugs. Disinhibitory drugs can engender increases in the (otherwise low) frequency of certain behaviors. Use of disinhibitory drugs is associated with a number of risk-taking behaviors leading to harmful outcomes -- including automobile accidents, vandalism, violent crimes, sexual assault, and risky sexual behavior. Importantly, use of disinhibitory drugs and the risky behavior that often follows is prevalent among younger adults. The social and behavioral consequences of drug-mediated risk taking in young adults are thus a considerable public health concern and a vital scientific endeavor. Studying the relationship between disinhibitory drugs and risk-taking behavior under controlled laboratory conditions will provide important scientific information. The experiments in this application propose to investigate changes in risk-taking following acute administration of four drugs abused by young adults: alcohol, marijuana, and the benzodiazepines alprazolam (Xanax) and flunitrazepam (Rohypnol). While many young adults use these drugs, not all abuse them, and not all engage in excessive risk-taking while under the influence. Thus, identification of basic behavioral processes and characteristics involved in risk-taking may help predict those whose behavior is most likely to be unduly influenced by drug use. Each of the four proposed experiments will employ a laboratory-based task to measure risk-taking. This task has been systematically developed over several years, and has been shown to be sensitive to (i) individual differences in risk-taking (in both adolescent and adult populations), and (ii) acute drug effects. Each participant will work on the risk-taking task following acute administration of one of the above-mentioned disinhibitory drugs. Using a within-subject design, a range of doses will administered in order to determine dose-effect relationships. Quantitative analyses of behavior patterns will be used to identify factors that may mediate this relationship.