Quednow Boris B, Csomor Philipp A, Chmiel Joelle, Beck Thilo, Vollenweider Franz X
University Hospital of Psychiatry, Experimental Psychopathology and Brain Imaging, University of Zurich, Switzerland.
Int J Neuropsychopharmacol. 2008 Aug;11(5):655-69. doi: 10.1017/S1461145707008322. Epub 2008 Jan 16.
Prepulse inhibition (PPI) of the acoustic startle response (ASR) has been established as an operational measure of sensorimotor gating. Animal and human studies have shown that PPI can be modulated by dopaminergic, serotonergic, and glutamatergic drugs and consequently it was proposed that impaired sensorimotor gating in schizophrenia parallels a central abnormality within the corresponding neurotransmitter systems. Recent animal studies suggest that the opioid system may also play a role in the modulation of sensorimotor gating. Thus, the present study investigated the influence of the mu-opioid receptor agonist morphine on PPI in healthy human volunteers. Eighteen male, non-smoking healthy volunteers each received placebo or 10 mg morphine sulphate (p.o.) at a 2-wk interval in a double-blind, randomized, and counterbalanced order. PPI was measured 75 min after drug/placebo intake. The effects of morphine on mood were measured by the Adjective Mood Rating Scale and side-effects were assessed by the List of Complaints. Additionally, we administered a comprehensive neuropsychological test battery consisting of tests of the Cambridge Neuropsychological Test Automated Battery and the Rey Auditory Verbal Learning Test. Morphine significantly increased PPI without affecting startle reactivity or habituation. Furthermore, morphine selectively improved the error rate in an attentional set-shifting task but did not influence vigilance, memory, or executive functions. These results imply that the opioid system is involved in the modulation of PPI and attentional set-shifting in humans and they raise the question whether the opioid system plays a crucial role also in the regulation of PPI and attentional set-shifting in schizophrenia.
听觉惊吓反应（ASR）的前脉冲抑制（PPI）已被确立为感觉运动门控的一种操作性测量指标。动物和人类研究表明，PPI可被多巴胺能、血清素能和谷氨酸能药物调节，因此有人提出精神分裂症中感觉运动门控受损与相应神经递质系统内的中枢异常相似。最近的动物研究表明，阿片系统也可能在感觉运动门控的调节中发挥作用。因此，本研究调查了μ-阿片受体激动剂吗啡对健康人类志愿者PPI的影响。18名男性、不吸烟的健康志愿者，每人以双盲、随机和平衡的顺序，每隔2周接受一次安慰剂或10毫克硫酸吗啡（口服）。在服用药物/安慰剂75分钟后测量PPI。通过形容词情绪评定量表测量吗啡对情绪的影响，并通过症状清单评估副作用。此外，我们进行了一套全面的神经心理学测试，包括剑桥神经心理学测试自动电池组测试和雷伊听觉词语学习测试。吗啡显著增加了PPI，而不影响惊吓反应性或习惯化。此外，吗啡选择性地改善了注意力转换任务中的错误率，但不影响警觉性、记忆力或执行功能。这些结果表明，阿片系统参与了人类PPI和注意力转换的调节，并且提出了阿片系统在精神分裂症中PPI和注意力转换的调节中是否也起关键作用的问题。
