Pietrowsky R, Thiemann A, Kern W, Fehm H L, Born J
Department of Clinical Neuroendocrinology, University of Lübeck, Germany.
Psychoneuroendocrinology. 1996 Aug;21(6):559-72. doi: 10.1016/s0306-4530(96)00012-1.
The access of substances to the brain is of particular relevance for the etiology and treatment of psychiatric and neurologic diseases. This study provides functional evidence for a direct access of peptides to the human brain after intranasal administration. Effects were compared of intranasal (IN, 10 micrograms) and intravenous (i.v., 0.25 and 2.5 micrograms) administered cholecystokinin-8 (CCK) on the auditory event related potential (AERP) in 20 healthy subjects. Also, plasma concentration of cortisol and ACTH were monitored. The study was designed as a placebo-controlled, double-blind within-subject cross-over comparison. AERPs were recorded while the subject performed on an attention task (oddball task). Plasma CCK concentrations after IN administration of CCK were comparable to those after i.v. administration of 0.25 microgram CCK, but were substantially lower than those after 2.5 micrograms CCK. The P3 complex of the AERP was markedly increased following the IN administration of CCK (p < .01) compared to placebo and to the i.v. administration of 0.25 microgram. This pattern was more obvious in women than men. Increases in plasma ACTH concentrations after CCK reached significance selectively following the IN mode of administration (p < .01).
物质进入大脑对于精神疾病和神经疾病的病因学及治疗具有特别重要的意义。本研究提供了功能证据，证明肽经鼻内给药后可直接进入人脑。比较了20名健康受试者经鼻内（IN，10微克）和静脉内（i.v.，0.25微克和2.5微克）给予胆囊收缩素-8（CCK）对听觉事件相关电位（AERP）的影响。此外，还监测了皮质醇和促肾上腺皮质激素的血浆浓度。该研究设计为安慰剂对照、双盲的受试者内交叉比较。在受试者执行注意力任务（oddball任务）时记录AERP。经鼻内给予CCK后的血浆CCK浓度与静脉内给予0.25微克CCK后的浓度相当，但远低于给予2.5微克CCK后的浓度。与安慰剂和静脉内给予0.25微克相比，经鼻内给予CCK后AERP的P3复合波明显增加（p <.01）。这种模式在女性中比在男性中更明显。CCK给药后血浆促肾上腺皮质激素浓度的增加仅在经鼻内给药方式下达到显著水平（p <.01）。
