McElroy J F, Miller J M, Meyer J S
J Pharmacol Exp Ther. 1984 Mar;228(3):593-9.
Serum corticosterone concentrations were measured in rats after injection of fenfluramine (FEN), p-chloroamphetamine (PCA) and p-fluoroamphetamine (PFA), halogenated amphetamine derivatives believed to exert their behavioral and physiological effects through the release and/or depletion of brain serotonin (5-HT). Animals were pretreated with various serotonergic drugs before FEN, PCA or PFA in order to ascertain the role of 5-HT in mediating the pituitary-adrenocortical response to each compound. Systemic administration of FEN, PCA or PFA caused a dose-dependent corticosterone elevation, with a potency rank ordering of PCA greater than FEN greater than PFA. Chronic depletion of brain 5-HT by pretreatment with p-chlorophenylalanine or 5,7-dihydroxytryptamine antagonized the PCA-induced elevation, but not that produced by FEN or PFA. When injected i.c.v., PCA and PFA elevated corticosterone levels whereas FEN did not. The central PCA-induced elevation was prevented by pretreatment with either the 5-HT reuptake inhibitor fluoxetine or the 5-HT receptor blocker methysergide. Fluoxetine or methysergide also antagonized the corticosterone elevation produced by systemically injected PCA or FEN, but not that produced by PFA. In the final experiment, pretreatment with dexamethasone, an inhibitor of pituitary adrenocorticotropic hormone secretion, prevented the corticosterone elevation produced by all three drugs. Thus, despite their structural and pharmacological similarities, FEN, PCA and PFA each act differently to stimulate corticosterone secretion. As expected, PCA elevates corticosterone levels through a central serotonergic mechanism that requires the continued synthesis and storage of 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS)
在给大鼠注射芬氟拉明（FEN）、对氯苯丙胺（PCA）和对氟苯丙胺（PFA）后，测定其血清皮质酮浓度。这几种卤代苯丙胺衍生物被认为是通过释放和/或消耗脑内5-羟色胺（5-HT）来发挥其行为和生理效应的。在注射FEN、PCA或PFA之前，先用各种血清素能药物对动物进行预处理，以确定5-HT在介导垂体-肾上腺皮质对每种化合物反应中的作用。全身性给予FEN、PCA或PFA会导致皮质酮剂量依赖性升高，其效力排序为PCA＞FEN＞PFA。用对氯苯丙氨酸或5,7-二羟基色胺预处理使脑内5-HT长期耗竭，可拮抗PCA诱导的皮质酮升高，但不能拮抗FEN或PFA诱导的升高。当脑室内注射时，PCA和PFA可升高皮质酮水平，而FEN则不能。预先用5-HT再摄取抑制剂氟西汀或5-HT受体阻滞剂美西麦角处理，可阻止中枢PCA诱导的皮质酮升高。氟西汀或美西麦角也可拮抗全身性注射PCA或FEN引起皮质酮升高，但不能拮抗PFA引起的升高。在最后一项实验中，用地塞米松（一种垂体促肾上腺皮质激素分泌抑制剂）预处理，可阻止这三种药物引起的皮质酮升高。因此，尽管FEN、PCA和PFA在结构和药理学上有相似之处，但它们刺激皮质酮分泌的作用方式各不相同。正如预期的那样，PCA通过一种需要持续合成和储存5-HT的中枢血清素能机制升高皮质酮水平。（摘要截短于250词）
