Mayerhofer A, Kovar K A, Schmidt W J
Zoological Institute, Neuropharmacology, University of Tuebingen, Ob dem Himmelreich 7, 72074 Tuebingen, Germany.
Neurosci Lett. 2001 Aug 3;308(2):99-102. doi: 10.1016/s0304-3940(01)01992-9.
The selective neurotoxic action of the abused drug 3,4-methylenedioxymethamphetamine (MDMA) on the serotonergic axons ascending from the dorsal raphe nucleus (DRN) is well known. The present study examined the long-term effects of subchronic MDMA treatment on rat brain tissue contents of catecholaminergic neurotransmitters. Two and four weeks after cessation of repeated MDMA treatment (ten consecutive days, 20 mg/kg/day), the tissue neurotransmitter concentrations were measured by means of electrochemical detected HPLC in several forebrain areas and DRN. We found reduced serotonin levels in the whole forebrain at both instants of time. In nucleus accumbens (NAC), the noradrenaline levels were also decreased, whereas dopamine levels were increased 4 weeks after treatment. It is concluded that MDMA causes changes of monoamine transmitter levels outlasting cessation of drug intake for at least 4 weeks. Decreased noradrenaline and/or serotonin may subsequently cause the augmentation of dopamine in NAC, a structure crucially involved in motivation circuits. With exception of transmitter alterations in the NAC, the post drug effects are opposite to the acute effects of MDMA and may underlie the psychiatric changes after MDMA intake in humans.
滥用药物3,4-亚甲基二氧甲基苯丙胺（摇头丸）对从背侧中缝核（DRN）上行的5-羟色胺能轴突具有选择性神经毒性作用，这是众所周知的。本研究考察了亚慢性摇头丸治疗对大鼠脑组织儿茶酚胺能神经递质含量的长期影响。在重复摇头丸治疗（连续十天，20毫克/千克/天）停止后两周和四周，通过电化学检测高效液相色谱法测量了几个前脑区域和DRN中的组织神经递质浓度。我们发现在这两个时间点，整个前脑的5-羟色胺水平均降低。在伏隔核（NAC）中，去甲肾上腺素水平也降低，而治疗四周后多巴胺水平升高。得出的结论是，摇头丸导致单胺递质水平的变化在药物摄入停止后至少持续四周。去甲肾上腺素和/或5-羟色胺减少可能随后导致NAC中多巴胺增加，NAC是一个在动机回路中起关键作用的结构。除了NAC中的递质改变外，药物后的效应与摇头丸的急性效应相反，可能是人类摄入摇头丸后精神变化的基础。
