Navarra Rachel L, Clark Brian D, Zitnik Gerard A, Waterhouse Barry D
Pharmacology and Physiology, Drexel University College of Medicine.
Exp Clin Psychopharmacol. 2013 Oct;21(5):363-74. doi: 10.1037/a0033563.
Attention deficits and inappropriate regulation of sensory signal processing are hallmarks of many neuropsychiatric conditions, including attention deficit hyperactivity, for which methylphenidate (MPH) and atomoxetine (ATX) are commonly prescribed therapeutic treatments. Despite their widespread use and known mechanism of blocking reuptake of catecholamine transmitters in the brain, the resultant actions on individual neuron and neural circuit function that lead to therapeutic efficacy are poorly understood. Given the ability of MPH and ATX to improve cognitive performance in humans and rodent assays of attention, we were interested in their influence on early sensory processing in the dorsal lateral geniculate nucleus (dLGN), the primary thalamic relay for visual information from the retina to the visual cortex. In male rats, dLGN neuronal responses to light stimuli were altered in multiple ways after doses of MPH or ATX observed to enhance performance in visually guided assays of attention (MPH = 2 mg/kg; ATX = 0.5 mg/kg). Latencies to response onset and to the peak of the primary response were decreased, while the peak intensity and area of the primary response were increased. In addition, some cells that were unresponsive to light stimuli prior to drug treatment displayed a "gating effect," wherein prominent responses to light stimuli were evident after drug administration. Our results begin to reveal unique effects of MPH and ATX in enhancing sensory signal transmission through visual circuitry, and may yield new insights for understanding the pathophysiology of certain cognitive disorders and inform development of improved therapeutic treatments for these conditions.
注意力缺陷和感觉信号处理的不当调节是许多神经精神疾病的特征，包括注意力缺陷多动障碍，对此哌甲酯（MPH）和托莫西汀（ATX）是常用的治疗药物。尽管它们被广泛使用且已知其阻断大脑中儿茶酚胺递质再摄取的机制，但导致治疗效果的对单个神经元和神经回路功能的最终作用仍知之甚少。鉴于MPH和ATX能够改善人类和啮齿动物注意力测试中的认知表现，我们对它们对背侧外侧膝状核（dLGN）早期感觉处理的影响感兴趣，dLGN是从视网膜到视觉皮层的视觉信息的主要丘脑中继站。在雄性大鼠中，在观察到MPH或ATX剂量（MPH = 2 mg/kg；ATX = 0.5 mg/kg）可提高视觉引导注意力测试中的表现后，dLGN神经元对光刺激的反应以多种方式发生改变。反应开始和初级反应峰值的潜伏期缩短，而初级反应的峰值强度和面积增加。此外，一些在药物治疗前对光刺激无反应的细胞表现出“门控效应”，即在给药后对光刺激有明显的反应。我们的结果开始揭示MPH和ATX在增强通过视觉回路的感觉信号传递方面的独特作用，并可能为理解某些认知障碍的病理生理学提供新的见解，并为开发针对这些疾病的改进治疗方法提供参考。
