Acute concomitant effects of MDMA binge dosing on extracellular 5-HT, locomotion and body temperature and the long-term effect on novel object discrimination in rats
Acute concomitant effects of MDMA binge dosing on extracellular 5-HT, locomotion and body temperature and the long-term effect on novel object discrimination in rats
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DOI：
10.1007/s00213-010-1921-9
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发表时间：
2011-02-01
影响因子：
3.4
通讯作者：
Fone, Kevin C. F.
中科院分区：
文献类型：
--
作者：
Rodsiri, Ratchanee;Spicer, Clare;Fone, Kevin C. F.
3，4-亚甲基二氧基甲基苯丙胺(MDMA，摇头丸)在大脑中产生5-羟色胺的急性释放，伴随着运动增加和体温升高。本研究探讨了运动活动和体温的急性功能变化是否与MDMA诱导的5-羟色胺释放增加有关。我们通过在体脑微透析同时测量神经元外5-羟色胺的变化，并使用放射遥测技术测量运动和体温，以确定这三个参数之间是否存在正相关。小剂量MDMA(3 mg/kg和6 mg/kg，间隔2-h三次)重复给药，提供与娱乐吸毒者相似的药物暴露。MDMA引起急性多动，核心体温变化(低温和高温)和海马5-羟色胺溢出升高，所有这些都依赖于MDMA的剂量。运动活动的改变和体温升高的幅度似乎彼此无关，也与MDMA诱导的5-羟色胺释放的幅度无关。这项研究还发现，在重复服用MDMA两周后，新对象辨别能力长期中断的证据。MDMA诱导的大脑中5-羟色胺的释放与体温过高或运动活动增加无关。由于MDMA在给药2周后均未引起5-羟色胺的神经毒性丧失，因此在新的物体辨别中发现的再认记忆障碍可能是其他长期变化的结果。
3,4-methylenedioxymethamphetamine (MDMA, ecstasy) produces an acute release of 5-HT in the brain, together with increased locomotion and hyperthermia.This study examined whether the acute functional changes of locomotor activity and body temperature are related to enhanced 5-HT release induced by MDMA.We concomitantly measured changes in extraneuronal 5-HT by in vivo brain microdialysis and used radiotelemetry to measure locomotion and body temperature to establish whether any positive correlations occur between these three parameters. 'Binge-type' repeated administration of low doses of MDMA (3 and 6 mg/kg given at 2-h intervals three times) were given to provide drug exposure similar to that experienced by recreational drug users.MDMA induced acute hyperactivity, changes in core body temperature (both hypothermia and hyperthermia) and elevation of hippocampal 5-HT overflow, all of which were dependent on the dose of MDMA administered. The change in locomotor activity and the magnitude of the hyperthermia appeared to be unrelated both to each other and to the magnitude of MDMA-induced 5-HT release. The study also found evidence of long-term disruption of novel object discrimination 2 weeks following "binge-type" repeated MDMA administration.MDMA-induced 5-HT release in the brain was not responsible for either the hyperthermia or increased locomotor activity that occurred. Since neither dose schedule of MDMA induced a neurotoxic loss of brain 5-HT 2 weeks after its administration, the impairment of recognition memory found in novel object discrimination probably results from other long-term changes yet to be established.