Alcohol Effects on Explicit Cue vs. Contextual Fear

描述（由申请人提供）：关于急性酒精影响的研究 对负面情绪的陶醉一直由应激反应主导 抑制的观点，这表明酒精减少了消极的情感， 通过直接药理学抑制对厌恶刺激的反应， 主要皮层下恐惧系统的活动。 但最近的 酒精对恐惧反应的不同影响的令人信服的证明 这取决于引发恐惧的线索的认知加工要求 这表明了一个更复杂的机制。 电流 恐惧神经回路动物模型的进展表明， 线索是通过多个平行的途径处理的， 皮层结构转化为初级皮层下恐惧系统， 不同的途径负责处理不同的特征 的线索。 综合这些神经科学发现与最近的 观察到的酒精对恐惧的影响的分离表明，酒精确实 不会直接影响初级皮层下防御系统， 它通过对特定环境的有害影响来影响恐惧。 认知评估某些神经元所需的皮层结构和途径 情感唤起的刺激。 目前的项目将研究人类的恐惧条件反射在醉酒和 非中毒个体，指数与恐惧增强惊吓（FPS），在 两种不同的提示条件。 这些条件将涉及1）线索 其需要更高阶的认知处理（例如，记忆上下文） 其由海马和附属脑结构介导（即， 情境恐惧条件）;或2）简单，明确的线索，不需要这样的 复杂处理（即，外显线索恐惧条件反射）。 大量的神经科学研究表明， 路径和认知系统/结构是发展所必需的 对这两组不同的线索产生条件性恐惧。 因此，酒精对恐惧的影响在这些线索中的解离 条件表明，这种药物对情绪的影响是由 特定的高级大脑过程和途径，而不是由大脑产生的。 直接作用于主要的恐惧系统 根据假设， 酒精间接影响情绪反应，通过其对 更高的排水区，包括海马，这一主要目的 实验是为了确定乙醇摄入是否选择性地损害 获得和/或表达的上下文条件反射，但离开 外显线索条件反射在人类身上完好无损

DESCRIPTION (provided by applicant): Research on the effects of acute alcohol intoxication on negative affect has been dominated by the Stress Response Dampening perspective, which suggests that alcohol reduces negative affective response to aversive stimuli through direct pharmacological suppression of activity in the primary subcortical fear system. However, recent compelling demonstrations of differential effects of alcohol on fear response dependent upon the cognitive processing requirements of the fear-eliciting cue suggest a more complex mechanism. Current advances in animal models of the neural circuitry of fear indicate that fear cues are processed through multiple, parallel pathways from subcortical and cortical structures into the primary subcortical fear system, with different pathways responsible for processing different characteristics of the cues. Synthesis of these neuroscience findings with the recent observed dissociations in alcohol's effect on fear suggests that alcohol does not directly affect the primary subcortical defensive system but instead exerts its influence on fear through its deleterious effects on specific cortical structures and pathways required for cognitive appraisal of certain emotionally evocative stimuli. The current project will examine human fear conditioning in intoxicated and non-intoxicated individuals, indexed with fear potentiated startle (FPS), in two distinct cuing conditions. These conditions will involve either 1) Cues which require higher-order cognitive processing (e.g., memory for context) that is mediated by the hippocampus and affiliated brain structures (i.e., contextual fear conditioning); or 2) Simpler, explicit cues not requiring such complex processing (i.e., explicit-cue fear conditioning). Substantial neuroscience research exists to indicate that different neural pathways and cognitive systems/structures are required for the development of conditioned fear to these two different sets of cues. Therefore, dissociation in alcohol's effect on fear across these cuing conditions would indicate that this drug's effect on emotion is mediated by specific higher brain processes and pathways, rather than produced by the direct action on the primary fear system. In line with the hypothesis that alcohol affects emotional responsivity indirectly, through its impact on higher Drain regions including the hippocampus, the primary aim of this experiment is to determine whether ethanol ingestion selectively impairs acquisition and/or expression of contextual conditioning, but leaves explicit-cue conditioning intact in humans.