Obradovic T, Imel K M, White S R
Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman, WA 99164, USA.
Brain Res. 1998 Feb 23;785(1):1-9. doi: 10.1016/s0006-8993(97)01337-1.
The purpose of this experiment was to investigate the effects of repeated exposure to methylenedioxymethamphetamine (MDMA) on responses of neurons in the nucleus accumbens of anesthetized rats to microiontophoretically-applied dopamine and serotonin. In tests conducted 1-4 days or 9-15 days following the last injection of MDMA (20 mg/kg, s.c., twice daily for 4 days), the inhibitory effects of both dopamine and serotonin on glutamate-evoked firing of nucleus accumbens cells were significantly attenuated compared to effects in control rats that were pretreated with saline injections. The inhibitory effect of the D1 receptor agonist SKF38393 was also significantly attenuated in the MDMA-pretreated rats. In contrast, the amount of inhibition of glutamate-evoked firing produced by application of GABA did not significantly differ between the MDMA-pretreated and the saline-pretreated rats. The neurotoxicity of the MDMA treatment regimen was confirmed by demonstrating that 3H-paroxetine binding was significantly decreased in the medial prefrontal cortex and the nucleus accumbens of the MDMA-pretreated rats. The mechanisms that produce the attenuated inhibitory responses to dopamine and serotonin following repeated injections of MDMA are not known. However, the results of these experiments indicate that repeated MDMA administration induces long-lasting changes in dopaminergic as well as serotonergic neurotransmission in the nucleus accumbens.
本实验的目的是研究反复接触亚甲基二氧甲基苯丙胺（摇头丸）对麻醉大鼠伏隔核中神经元对微量离子电泳施加的多巴胺和5-羟色胺反应的影响。在最后一次注射摇头丸（20毫克/千克，皮下注射，每日两次，共4天）后的1 - 4天或9 - 15天进行的测试中，与用盐水注射预处理的对照大鼠相比，多巴胺和5-羟色胺对伏隔核细胞谷氨酸诱发放电的抑制作用均显著减弱。在经摇头丸预处理的大鼠中，D1受体激动剂SKF38393的抑制作用也显著减弱。相比之下，应用γ-氨基丁酸（GABA）对谷氨酸诱发放电的抑制量在经摇头丸预处理和经盐水预处理的大鼠之间没有显著差异。通过证明经摇头丸预处理的大鼠内侧前额叶皮质和伏隔核中3H-帕罗西汀结合显著减少，证实了摇头丸治疗方案的神经毒性。反复注射摇头丸后对多巴胺和5-羟色胺产生减弱的抑制反应的机制尚不清楚。然而，这些实验结果表明，反复给予摇头丸会在伏隔核中诱导多巴胺能和5-羟色胺能神经传递的长期变化。
