长期暴露于摇头丸的大鼠体外神经元和血管对5-羟色胺的反应。

In vitro neuronal and vascular responses to 5-HT in rats chronically exposed to MDMA.

作者信息

Cannon D M, Keenan A K, Guiry P J, Buon C, Baird A W, McBean G J

机构信息

Department of Pharmacology, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.

出版信息

Br J Pharmacol. 2001 Dec;134(7):1455-60. doi: 10.1038/sj.bjp.0704402.

DOI:10.1038/sj.bjp.0704402

PMID:11724751

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1573088/

Abstract

This study examined the effects of chronic exposure of rats to 3,4-methylenedioxymethamphetamine (MDMA) on [(3)H]5-hydroxytryptamine ([(3)H]5-HT) re-uptake into purified rat brain synaptosomes, 5-HT-induced isometric contraction of aortic rings and [(3)H]5-HT re-uptake into rat aorta. 2. Rats were administered MDMA (20 mg kg(-1) i.p.) twice daily over 4 days. One, 7, 14 or 21 days post treatment, whole brain synaptosomes and descending thoracic aortic rings were prepared for investigation. 3. Chronic MDMA treatment significantly reduced the maximum rate (V(max)) of specific high-affinity [(3)H]5-HT re-uptake 1 day after treatment and for up to 21 days post-final administration of MDMA. Direct application of MDMA (100 microM) abolished synaptosomal re-uptake of [(3)H]5-HT in vitro. 4. Chronic MDMA administration significantly reduced the maximum contraction (E(max)) to 5-HT at 1 and 7 days after treatment, but not at 14 or 21 days. 5. Chronic MDMA administration had no effect on sodium-dependent [(3)H]5-HT re-uptake into aorta 1 day after treatment, nor did 100 microM MDMA have any direct effect on [(3)H]5-HT uptake into aortic rings in vitro. 6. These results show, for the first time, an altered responsiveness of vascular tissue to MDMA after chronic administration. In addition, they demonstrate a difference in the sensitivity of central and peripheral 5-HT uptake systems to chronic MDMA exposure, and suggest that the action of MDMA in the cardiovascular system does not arise from a direct effect of MDMA on peripheral 5-HT transport.

摘要

本研究检测了大鼠长期暴露于3,4-亚甲基二氧甲基苯丙胺（摇头丸）对纯化的大鼠脑突触体中[³H]5-羟色胺（[³H]5-HT）再摄取、5-HT诱导的主动脉环等长收缩以及大鼠主动脉中[³H]5-HT再摄取的影响。2. 大鼠每天腹腔注射两次摇头丸（20 mg kg⁻¹），持续4天。在治疗后1、7、14或21天，制备全脑突触体和胸降主动脉环用于研究。3. 长期给予摇头丸治疗后1天以及末次给药后长达21天，特异性高亲和力[³H]5-HT再摄取的最大速率（V(max)）显著降低。在体外直接应用摇头丸（100 μM）可消除[³H]5-HT的突触体再摄取。4. 长期给予摇头丸治疗后1天和7天，对5-HT的最大收缩（E(max)）显著降低，但在14天或21天时未降低。5. 长期给予摇头丸治疗后1天，对主动脉中钠依赖性[³H]5-HT再摄取无影响，100 μM摇头丸在体外对主动脉环中[³H]5-HT摄取也无直接影响。6. 这些结果首次表明，长期给药后血管组织对摇头丸的反应性发生改变。此外，它们还证明了中枢和外周5-HT摄取系统对长期暴露于摇头丸的敏感性存在差异，并表明摇头丸在心血管系统中的作用并非源于其对外周5-HT转运的直接影响。