Peat M A, Warren P F, Gibb J W
J Pharmacol Exp Ther. 1983 Apr;225(1):126-31.
A single dose (17.5 mg/kg i.p.) of methamphetamine was administered to iprindole-treated (10 mg/kg i.p.) rats. Forebrain concentrations of methamphetamine and amphetamine were significantly increased in iprindole-treated rats 1 and 6 hr after injection; in contrast to rats pretreated with saline, both amines were also detected after 18 hr. Three and 7 days after injection, significant decreases were seen in tryptophan hydroxylase (TPH) activity and serotonin concentrations in the cerebral cortex, neostriatum and hypothalamus. Hypothalamic TPH activity had recovered by 14 days. Neostriatal tyrosine hydroxylase activity and dopamine concentrations were significantly depressed at all time points examined. Iprindole alone produced a significant increase in cortical TPH activity after 1 day. After 3 days, TPH activity was significantly decreased when compared with control, whereas serotonin and 5-hydroxyindoleacetic acid concentrations were significantly increased. This study demonstrates that persistence of methamphetamine and/or amphetamine at the site of action is important for neurotoxicity.
给经伊普吲哚处理（腹腔注射10 mg/kg）的大鼠腹腔注射单剂量（17.5 mg/kg）甲基苯丙胺。注射后1小时和6小时，经伊普吲哚处理的大鼠前脑甲基苯丙胺和苯丙胺浓度显著升高；与用生理盐水预处理的大鼠相比，18小时后也检测到了这两种胺类物质。注射后3天和7天，大脑皮层、新纹状体和下丘脑的色氨酸羟化酶（TPH）活性和血清素浓度显著降低。下丘脑TPH活性在14天时恢复。在所有检测时间点，新纹状体酪氨酸羟化酶活性和多巴胺浓度均显著降低。单独使用伊普吲哚1天后可使皮层TPH活性显著增加。3天后，与对照组相比，TPH活性显著降低，而血清素和5-羟吲哚乙酸浓度显著升高。本研究表明，甲基苯丙胺和/或苯丙胺在作用部位的持续存在对神经毒性很重要。
