Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands.
Psychopharmacology (Berl). 2013 Jan;225(2):303-12. doi: 10.1007/s00213-012-2817-7. Epub 2012 Aug 2.
Sensory gating is an adaptive mechanism of the brain to prevent overstimulation. Patients suffering from clinical disorders such as Alzheimer's disease or schizophrenia exhibit a deficit in gating, which indicates not only an impairment in basic information processing that might contribute to the cognitive problems seen in these patients. Phosphodiesterase type 5 inhibitors (PDE5-Is) have been shown to improve cognition in rodents in various behavioural tasks and might consequently be an interesting target for cognition enhancement. However, the effects of PDE5-Is on sensory gating are not known yet.
This work aims to study the effects of PDE5 inhibition on auditory sensory gating in rats and humans.
In the rat study, vehicle or 0.3-3 mg/kg of the PDE5-I vardenafil was given orally 30 min before testing and electrode locations were the vertex, hippocampus and the striatum. The human subjects received placebo, 10-20 mg vardenafil 85 min before testing and sensory gating was measured at the cortex (Fz, Fcz and Cz) electrodes.
Significant gating was only found for the N1 component in rats while all three peaks P1, N1 and P2 showed gating in humans, i.e. the response to the second sound click was decreased as compared with the first for these deflections. Administration of vardenafil did neither have an effect on sensory gating in rats nor in humans.
These findings imply that positive effects of PDE5 inhibition on cognition are not mediated by more early phases of information processing.
感觉门控是大脑的一种自适应机制，可防止过度刺激。患有阿尔茨海默病或精神分裂症等临床疾病的患者表现出门控缺陷，这不仅表明基本信息处理受损，而这种受损可能导致这些患者出现认知问题。磷酸二酯酶 5 抑制剂（PDE5-Is）已被证明可改善各种行为任务中小鼠的认知能力，因此可能是增强认知的一个有趣目标。然而，PDE5-Is 对感觉门控的影响尚不清楚。
本研究旨在研究 PDE5 抑制对大鼠和人类听觉感觉门控的影响。
在大鼠研究中，在测试前 30 分钟给予载体或 0.3-3mg/kg 的 PDE5-I 伐地那非口服，电极位置为顶点、海马体和纹状体。人类受试者接受安慰剂，在测试前 85 分钟给予 10-20mg 伐地那非，在 Fz、Fcz 和 Cz 电极处测量感觉门控。
在大鼠中仅发现 N1 成分有明显的门控，而在人类中，所有三个峰 P1、N1 和 P2 都显示出门控，即与第一个声音点击相比，这些波幅的第二个声音点击的反应降低。伐地那非给药既没有影响大鼠也没有影响人类的感觉门控。
这些发现表明，PDE5 抑制对认知的积极影响不是通过信息处理的早期阶段介导的。
