Baldessarini R J, Marsh E R, Kula N S
Department of Psychiatry, Harvard Medical School, McLean Division of Massachusetts General Hospital, Belmont 02178.
Brain Res. 1992 May 1;579(1):152-6. doi: 10.1016/0006-8993(92)90754-w.
Given evidence of inhibitory effects of serotonin on dopaminergic neurotransmission, a series of experiments sought neurochemical evidence of interactions between the selective serotonin transport inhibitor fluoxetine and the metabolism of dopamine (DA) or serotonin (5-HT) in regions of rat brain that might account for extrapyramidal side-effects associated with clinical use of fluoxetine. There were significant inhibitory effects of acute or repeated fluoxetine treatment on the turnover of 5-HT (accumulation of 5-hydroxytryptophan, or ratio of [5-hydroxyindoleacetic acid]/[5-HT]) in striatum, nucleus accumbens and frontal cerebral cortex, but only minor effects on metabolism of DA (accumulation of dihydroxyphenylalanine, or [homovanillic acid]/[DA] ratio), even at high doses or with repeated treatment, and no significant inhibition of the DA metabolism-increasing actions of haloperidol.
鉴于血清素对多巴胺能神经传递具有抑制作用，一系列实验旨在寻找神经化学证据，以证明选择性血清素转运抑制剂氟西汀与大鼠脑区中多巴胺（DA）或血清素（5-HT）代谢之间的相互作用，这些相互作用可能是氟西汀临床使用中锥体外系副作用的原因。急性或重复给予氟西汀治疗对纹状体、伏隔核和额叶皮质中5-HT的周转（5-羟色氨酸的积累，或[5-羟吲哚乙酸]/[5-HT]比值）有显著抑制作用，但对DA代谢（二羟基苯丙氨酸的积累，或[高香草酸]/[DA]比值）仅有轻微影响，即使在高剂量或重复治疗时也是如此，并且对氟哌啶醇增加DA代谢的作用没有显著抑制。
