Labarca R, Thomas J W, Koulu M, Kim Y S, Janowsky A, Wilkinson L, Linnoila M, Paul S M, Pickar D
Clinical Neuroscience Branch, National Institute of Mental Health, Bethesda, MD 20892.
Brain Res Bull. 1988 May;20(5):567-71. doi: 10.1016/0361-9230(88)90215-8.
Plasma and brain levels of the dopamine metabolite, homovanillic acid, were measured in rats after acute and chronic treatment with fluphenazine. After acute administration, homovanillic acid levels were increased in the whole frontal cortex, caudate nucleus, nucleus accumbens, anterior cingulate (supragenual) cortex, prefrontal cortex and plasma. Following chronic administration, the effects of single doses of fluphenazine in increasing homovanillic acid were markedly attenuated in the caudate nucleus, nucleus accumbens, the whole frontal cortex, anterior cigulate cortex and plasma, but not in the prefrontal (anteromedial) cortex. Following fluphenazine administration plasma homovanillic acid levels were correlated with homovanillic acid concentrations in whole frontal cortex (r = 0.63, p less than 0.01) and caudate nucleus (r = 0.51, p less than 0.05). Further, prior intracerebroventricular administration of 6-hydroxydopamine prevented the fluphenazine-induced increase in plasma homovanillic acid. These data suggest that in the rat, plasma and brain (caudate nucleus and whole frontal cortex) homovanillic acid levels change in a similar fashion during acute and chronic neuroleptic administration.
在用氟奋乃静对大鼠进行急性和慢性治疗后，测定了多巴胺代谢物高香草酸的血浆和脑内水平。急性给药后，全额叶皮质、尾状核、伏隔核、前扣带回（膝上）皮质、前额叶皮质和血浆中的高香草酸水平升高。慢性给药后，单剂量氟奋乃静升高高香草酸的作用在尾状核、伏隔核、全额叶皮质、前扣带回皮质和血浆中明显减弱，但在前额叶（前内侧）皮质中未减弱。给予氟奋乃静后，血浆高香草酸水平与全额叶皮质（r = 0.63，p < 0.01）和尾状核（r = 0.51，p < 0.05）中的高香草酸浓度相关。此外，预先脑室内注射6-羟基多巴胺可阻止氟奋乃静引起的血浆高香草酸升高。这些数据表明，在大鼠中，急性和慢性给予抗精神病药物期间，血浆和脑（尾状核和全额叶皮质）中的高香草酸水平以相似的方式变化。
