Sloviter R S, Drust E G, Connor J D
J Pharmacol Exp Ther. 1978 Aug;206(2):348-52.
In the rat, d-amphetamine sulfate (15--80 mg/kg) causes numerous behavioral effects including simultaneous side-to-side head weaving or head tremor, forepaw padding and splayed hindlimbs. These signs are strikingly similar to a behavioral syndrome caused by intense serotonin (5-HT) receptor activation. Experiments were designed to determine whether some of the numerous effects of amphetamine on behavior can be ascribed to actions of the drug on 5-HT mechanisms. Catecholamine depletion with alpha-methyl-p-tyrosine did not prevent the amphetamine syndrome. However, 5-HT depletion with 5,7-dihydroxytryptamine or with p-chlorophenylalanine did prevent the syndrome. The degree of syndrome inhibition by p-chlorophenylalanine was correlated with the extent of 5-HT depletion. Normal responsiveness to amphetamine in p-chlorophenylalanine-treated rats was restored by 5-hydroxytryptophan, the precursor of 5-HT. Furthermore, methysergide, a 5-HT receptor blocker, prevented the amphetamine syndrome, whereas catecholamine blockers, phenoxybenzamine and pimozide, were ineffective. The results suggest that when amphetamine causes the signs of the syndrome it does so by activating 5-HT receptors in the brain, probably by displacement of endogenous 5-HT.
在大鼠中，硫酸右苯丙胺（15 - 80毫克/千克）会引发多种行为效应，包括同时左右摇头或头部震颤、前爪拍打以及后肢叉开。这些症状与强烈的血清素（5 - 羟色胺，5-HT）受体激活所导致的行为综合征极为相似。实验旨在确定苯丙胺对行为的众多影响中，是否有一些可归因于该药物对5-HT机制的作用。用α-甲基-对-酪氨酸使儿茶酚胺耗竭并不能预防苯丙胺综合征。然而，用5,7 - 二羟色胺或对氯苯丙氨酸使5-HT耗竭则可预防该综合征。对氯苯丙氨酸抑制综合征的程度与5-HT耗竭的程度相关。5 - 羟色胺的前体5 - 羟色氨酸可使经对氯苯丙氨酸处理的大鼠恢复对苯丙胺的正常反应性。此外，5-HT受体阻断剂麦角新碱可预防苯丙胺综合征，而儿茶酚胺阻断剂酚苄明和匹莫齐特则无效。结果表明，当苯丙胺引发该综合征的症状时，可能是通过取代内源性5-HT来激活大脑中的5-HT受体。
