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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Effects of (+)-fenfluramine on 3,4-methylenedioxymethamphetamine (MDMA) discrimination in rats.
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Effects of (+)-fenfluramine on 3,4-methylenedioxymethamphetamine (MDMA) discrimination in rats.

机译：（+）芬氟拉明对大鼠3,4-亚甲二氧基甲基苯丙胺（MDMA）区分的影响。

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This study examined the effects of a presumed neurotoxic dose regimen of (+)-fenfluramine on the discrimination of MDMA and (+)-amphetamine in male Sprague-Dawley rats trained to discriminate 1.5 mg/kg MDMA from saline in a two-choice operant task. Substitution tests were conducted with saline, several doses of MDMA (0.19-1.5 mg/kg), and (+)-amphetamine (0.125-1.0 mg/kg) prior to and again following the administration of (+)-fenfluramine (4.0 mg/kg twice a day for 4 days; n = 11) or a similar pattern of saline injections (n = 10). During pretreatment substitution tests, lower doses of MDMA elicited drug-appropriate responding in a dose-dependent manner, although none of these doses substituted for the training dose. Likewise, no dose of (+)-amphetamine substituted for the training drug during pretreatment substitution tests. The discrimination of MDMA was disrupted in some animals following (+)-fenfluramine treatment, but with subsequent training, discrimination criteria were met. In posttreatment substitution tests, the lowest dose of MDMA produced significantly higher drug-appropriate responding in (+)-fenfluramine treated animals but not in saline-treated animals. The amount of drug-appropriate responding during posttreatment substitution tests with (+)-amphetamine varied little from pretreatment substitution tests in saline-treated animals, but was greater at all doses in (+)-fenfluramine-treated animals; the highest dose of (+)-amphetamine substituted for MDMA subsequent to (+)-fenfluramine treatment. These results support previous findings that the long-lasting serotonergic effects of fenfluramine may have functional consequences that can be detected using a drug discrimination procedure. Specifically, serotonin depletion may unmask or strengthen the stimulant-like effects of MDMA.
机译：这项研究检查了假定的神经毒性剂量方案（+）-芬氟拉明对受过训练的雄性Sprague-Dawley大鼠的MDMA和（+）-苯异丙胺的辨别力的影响，该大鼠在两种选择中均已从盐水中区分出1.5 mg / kg MDMA。任务。在施用（+）芬氟拉明（4.0 mg）之前和之后，分别用生理盐水，几种剂量的MDMA（0.19-1.5 mg / kg）和（+）-苯异丙胺（0.125-1.0 mg / kg）进行替代测试。 / kg，每天两次，共4天; n = 11）或类似剂量的盐水注射（n = 10）。在预处理替代测试期间，较低剂量的MDMA以剂量依赖性方式引起药物适当的反应，尽管这些剂量均不能替代训练剂量。同样，在预处理替代测试期间，没有剂量的（+）-苯丙胺替代培训药物。 （+）芬氟拉明治疗后，某些动物对MDMA的辨别力遭到破坏，但经过后续训练，符合辨别标准。在治疗后替代测试中，最低剂量的MDMA在（+）芬氟拉明治疗的动物中产生明显更高的药物适当反应，但在盐水治疗的动物中则没有。 （+）-苯异丙胺在治疗后替代试验中与药物适当反应的量与盐水治疗动物中的治疗前替代试验相差不大，但在（+）-芬氟拉明治疗的动物中，所有剂量的药物响应量均较大。 （+）-苯氟拉明治疗后最高剂量的（+）-苯丙胺取代了MDMA。这些结果支持了以前的发现，即芬氟拉明的长期血清素作用可能会产生功能性后果，可以使用药物鉴别程序来检测。具体而言，5-羟色胺的消耗可能会掩盖或增强MDMA的类似刺激物的作用。

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