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长期给予去甲雄酮可减少大鼠伏隔核内可卡因诱导的多巴胺和 5-羟色胺释放。

Subchronic nandrolone administration reduces cocaine-induced dopamine and 5-hydroxytryptamine outflow in the rat nucleus accumbens.

机构信息

Department of Alcohol, Drugs and Addiction, National Institute for Health and Welfare, P.O. Box 30, 00271, Helsinki, Finland.

出版信息

Psychopharmacology (Berl). 2010 Apr;209(3):271-81. doi: 10.1007/s00213-010-1796-9. Epub 2010 Feb 26.

Abstract

RATIONALE

The abuse of anabolic androgenic steroids (AASs) is not only a problem in the world of sports but is associated with the polydrug use of nonathletes. Investigations of the neurochemical effects of AAS have focused in part on the monoaminergic systems, involving, among other things, the development of dependence. We have previously shown that pretreatment with nandrolone decanoate attenuates dose-dependently the increase in extracellular dopamine (DA) concentration evoked by amphetamine and 3,4-methylenedioyxymethamphetamine in the nucleus accumbens (NAc).

OBJECTIVES

The aim of this study was to investigate whether the nandrolone pre-exposure modulates the acute neurochemical and behavioral effects of cocaine in rats and whether the effects are long lasting.

METHODS

DA, 5-hydroxytryptamine (5-HT), and their metabolites were measured from samples collected from the NAc by microdialysis. The behavior of the animals was recorded.

RESULTS

The present study demonstrates that five injections of nandrolone (5 and 20 mg/kg) inhibited cocaine-evoked DA and 5-HT outflow in the NAc, locomotor activity (LMA), and stereotyped behavior in experimental animals, and that these effects are seen even after elimination of nandrolone from bloodstream.

CONCLUSIONS

Given that accumbal outflow of DA and 5-HT, as well as LMA and stereotyped behavior, is related to gratification of stimulant drugs, this study suggests that nandrolone, at the doses tested, has a significant effect on the pleasurable properties of cocaine. Furthermore, because neurochemical and behavioral responses were still attenuated after a fairly long recovery period, it seems that nandrolone may induce long-lasting changes in the brains of rat.

摘要

背景

滥用合成代谢雄激素(AAS)不仅是体育界的一个问题,而且与非运动员的多药滥用有关。对 AAS 的神经化学作用的研究部分集中在单胺能系统上,除其他外,还涉及依赖性的发展。我们之前已经表明,癸酸诺龙预处理可剂量依赖性地减弱安非他命和 3,4-亚甲基二氧基甲基苯丙胺在伏隔核(NAc)中引起的细胞外多巴胺(DA)浓度的增加。

目的

本研究旨在探讨癸酸诺龙预处理是否调节可卡因对大鼠的急性神经化学和行为效应,以及这些效应是否持久。

方法

通过微透析从 NAc 采集的样本中测量 DA、5-羟色胺(5-HT)及其代谢物。记录动物的行为。

结果

本研究表明,五次注射癸酸诺龙(5 和 20mg/kg)抑制了 NAc 中可卡因诱发的 DA 和 5-HT 流出、运动活动(LMA)和实验动物的刻板行为,并且这些效应甚至在血液中消除了诺龙后仍可见。

结论

鉴于 NAc 中 DA 和 5-HT 的流出以及 LMA 和刻板行为与兴奋剂的满足感有关,因此该研究表明,在测试剂量下,诺龙对可卡因的愉悦特性具有显著影响。此外,由于神经化学和行为反应在相当长的恢复期后仍被减弱,似乎诺龙可能会在大鼠的大脑中引起持久的变化。

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