Baumann Michael H, Clark Robert D, Rothman Richard B
Clinical Psychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, United States.
Pharmacol Biochem Behav. 2008 Aug;90(2):208-17. doi: 10.1016/j.pbb.2008.02.018. Epub 2008 Mar 4.
(+/-)-3,4-Methylenedioxymethamphetamine (MDMA, or Ecstasy) is an illicit drug that evokes transporter-mediated release of monoamines, including serotonin (5-HT) and dopamine (DA). Here we monitored the effects of MDMA on neurochemistry and motor activity in rats, as a means to evaluate relationships between 5-HT, DA, and behavior. Male rats undergoing in vivo microdialysis were housed in chambers equipped with photobeams for measurement of ambulation (i.e., forward locomotion) and stereotypy (i.e., head weaving and forepaw treading). Microdialysis probes were placed into the n. accumbens, striatum or prefrontal cortex in separate groups of rats. Dialysate samples were assayed for 5-HT and DA by microbore HPLC-ECD. Rats received two i.v. injections of MDMA, 1 mg/kg followed by 3 mg/kg 60 min later; neurochemical and locomotor parameters were measured concurrently. MDMA produced dose-related elevations in extracellular 5-HT and DA in all regions, with the magnitude of 5-HT release always exceeding that of DA release. MDMA-induced ambulation was positively correlated with dialysate DA levels in all regions (P<0.05-0.0001) and with dialysate 5-HT in striatum and cortex (P<0.001-0.0001). Stereotypy was strongly correlated with dialysate 5-HT in all areas (P<0.001-0.0001) and with dialysate DA in accumbens and striatum (P<0.001-0.0001). These data support previous work and suggest the complex spectrum of behaviors produced by MDMA involves 5-HT and DA in a region- and modality-specific manner.
（±）-3,4-亚甲基二氧甲基苯丙胺（摇头丸，或迷幻药）是一种非法药物，它能引发转运体介导的单胺类物质释放，包括5-羟色胺（5-HT）和多巴胺（DA）。在此，我们监测了摇头丸对大鼠神经化学和运动活动的影响，作为评估5-羟色胺、多巴胺和行为之间关系的一种手段。接受体内微透析的雄性大鼠被安置在配备有光束的实验箱中，用于测量行走（即向前运动）和刻板行为（即头部摆动和前爪踩踏）。将微透析探针分别植入不同组大鼠的伏隔核、纹状体或前额叶皮质。通过微径高效液相色谱-电化学检测法测定透析液样本中的5-羟色胺和多巴胺。大鼠静脉注射两次摇头丸，一次1毫克/千克，60分钟后再注射3毫克/千克；同时测量神经化学和运动参数。摇头丸在所有区域均导致细胞外5-羟色胺和多巴胺呈剂量相关的升高，5-羟色胺释放的幅度始终超过多巴胺释放的幅度。摇头丸诱导的行走与所有区域的透析液多巴胺水平呈正相关（P<0.05 - 0.0001），与纹状体和皮质中的透析液5-羟色胺呈正相关（P<0.001 - 0.0001）。刻板行为与所有区域的透析液5-羟色胺密切相关（P<0.001 - 0.0001），与伏隔核和纹状体中的透析液多巴胺密切相关（P<0.001 - 0.0001）。这些数据支持了先前的研究工作，并表明摇头丸产生的复杂行为谱以区域和方式特异性的方式涉及5-羟色胺和多巴胺。
