Lambert G W, Horne M, Kalff V, Kelly M J, Turner A G, Cox H S, Jennings G L, Esler M D
Human Autonomic Function Laboratory, Baker Medical Research Institute, Prahran Victoria, Australia.
Life Sci. 1995;56(19):1545-55. doi: 10.1016/0024-3205(95)00120-u.
The objective of this study was to obtain direct neurochemical measures of the central nervous system's response to a typical neuroleptic, haloperidol, in human subjects. Nine healthy volunteers participated in this study. Central nervous system neuronal activity was assessed by measuring the plasma concentration and overflow from the brain of dopamine, norepinephrine, and their lipophilic and acidic metabolites after acute intravenous administration of haloperidol. By combining bilateral internal jugular vein blood sampling with cerebral blood flow scans we were able to differentiate between cortical and subcortical responses to haloperidol. The central nervous system response to haloperidol administration displayed a degree of regional specificity. Dopamine release, estimated from the overflow of homovanillic and dihydroxyphenylacetic acids, was reduced in cortical but not subcortical brain regions. Norepinephrine turnover was increased in cortical and subcortical brain regions. The overflow of homovanillic acid from the brain into the internal jugular veins was not related quantitatively to the arterial plasma concentrations of the catecholamines examined, homovanillic and dihydroxyphenylacetic acids or prolactin. Measurements of catecholamines and their metabolites in arterial plasma gave little indication as to monoaminergic neuronal activity in the brain.
本研究的目的是获取人体受试者中枢神经系统对典型抗精神病药物氟哌啶醇反应的直接神经化学指标。九名健康志愿者参与了本研究。通过在急性静脉注射氟哌啶醇后测量多巴胺、去甲肾上腺素及其亲脂性和酸性代谢产物的血浆浓度和脑内溢出量，评估中枢神经系统神经元活性。通过将双侧颈内静脉采血与脑血流扫描相结合，我们能够区分皮质和皮质下对氟哌啶醇的反应。中枢神经系统对氟哌啶醇给药的反应表现出一定程度的区域特异性。根据高香草酸和二羟基苯乙酸的溢出量估计，皮质脑区的多巴胺释放减少，而皮质下脑区未减少。皮质和皮质下脑区的去甲肾上腺素周转率增加。脑内高香草酸向颈内静脉的溢出量与所检测的儿茶酚胺、高香草酸和二羟基苯乙酸或催乳素的动脉血浆浓度在数量上无关。动脉血浆中儿茶酚胺及其代谢产物的测量对脑内单胺能神经元活性的指示作用很小。
