Department of Cell Biology and Neuroscience, Rowan University School of Medicine, Stratford, NJ 08084, USA.
Department of Cell Biology and Neuroscience, Rowan University School of Medicine, Stratford, NJ 08084, USA.
Brain Res. 2019 Apr 15;1709:67-80. doi: 10.1016/j.brainres.2018.06.027. Epub 2018 Jun 21.
Prescription stimulants are used to treat attention deficit hyperactivity disorder (ADHD). Psychostimulants are also used off-label by non-ADHD patients as performance-enhancing agents across academic, occupational, athletic, and social settings. Extensive work has focused on the reinforcing effects and abuse liability of psychostimulants, but understanding the mechanisms through which these agents regulate neural circuit functions that govern cognitive and sensorimotor processes to result in their performance-enhancing effects has received less attention. Optimal detection of sensory information within complex, dynamic environments is critical for appropriate decision making and executive actions. As such, overall performance enhancement may significantly rely on improvements in the processing of incoming sensory stimuli. Psychostimulants enhance catecholamine neurotransmission through the blockade of dopamine and norepinephrine (NE) reuptake transporters. The ascending locus coeruleus (LC)-NE system regulates behavioral state and modulates state dependent transmission of sensory signals. LC stimulation and local administration of NE to sensory processing areas of the brain can change the dynamics of both cellular and circuit activity in response to incoming sensory information. Here we explore the LC-NE system's neuromodulatory role in altering sensory signal processing as a plausible mechanism through which psychostimulant agents amplify physiological responses to important sensory stimuli as a component of their performance-enhancing effects in both ADHD patients and otherwise healthy individuals. We further consider sensory enhancement as a desirable outcome that has not previously been explored as an element of therapeutic efficacy, as well as added motivation for otherwise healthy individuals to engage in off-label self-administration of psychostimulant drugs.
处方兴奋剂被用于治疗注意力缺陷多动障碍（ADHD）。精神兴奋剂也被非 ADHD 患者在学术、职业、运动和社交环境中用作表现增强剂。大量工作集中在精神兴奋剂的强化作用和滥用倾向，但理解这些药物调节神经回路功能的机制，这些功能控制认知和感觉运动过程，从而产生其表现增强作用，这方面的研究还比较少。在复杂、动态的环境中最佳地检测感觉信息对于适当的决策和执行动作至关重要。因此，整体表现的增强可能在很大程度上依赖于传入感觉刺激的处理改善。精神兴奋剂通过阻断多巴胺和去甲肾上腺素（NE）再摄取转运体来增强儿茶酚胺神经传递。上行蓝斑核（LC）-NE 系统调节行为状态，并调节感觉信号的状态依赖性传递。LC 刺激和 NE 局部给药到大脑的感觉处理区域，可以改变对传入感觉信息的细胞和电路活动的动力学。在这里，我们探讨了 LC-NE 系统在改变感觉信号处理中的神经调节作用，作为一种可能的机制，通过这种机制，精神兴奋剂药物放大对重要感觉刺激的生理反应，作为其在 ADHD 患者和其他健康个体中增强表现作用的组成部分。我们进一步考虑感觉增强作为一个以前没有被探索过的治疗效果的元素，以及作为健康个体非标签自我管理精神兴奋剂药物的额外动机。
