Widespread reduction of dopamine cell bodies and terminals in adult rats exposed to a low dose regimen of MDMA during adolescence
Widespread reduction of dopamine cell bodies and terminals in adult rats exposed to a low dose regimen of MDMA during adolescence
复制标题
DOI：
10.1016/j.neuropharm.2017.06.008
复制
发表时间：
2017-09-01
影响因子：
4.7
通讯作者：
Di Chiara, Gaetano
中科院分区：
文献类型：
--
作者：
Cadoni, Cristina;Pisanu, Augusta;Di Chiara, Gaetano
虽然MDMA（3，4-亚甲二氧基甲基苯丙胺，摇头丸）对5-羟色胺神经元的神经毒性在包括人类在内的多种物种中得到广泛认可，但多巴胺（DA）神经元的神经毒性被认为具有物种特异性。MDMA主要由青少年消费，通常与咖啡因（能量饮料）一起消费，据报告，这种关联加剧了MDMA的毒性作用。为了模拟MDMA使用的这些方面，相对维斯其对DA神经元的影响，我们研究了青少年暴露于低剂量MDMA（5 mg/kg，持续10天），单独或与咖啡因（10 mg/kg）结合对成年大鼠神经元和功能性DA指数以及识别记忆的影响。MDMA减少密度的酪氨酸羟化酶（TH）阳性神经元在腹侧被盖区和黑质pars腹侧区，和TH和DA转运蛋白的免疫反应性的核中脑（NAc）壳和核心，尾壳核。相同的治疗导致NAc核心中基础透析液DA减少。MDMA预处理的大鼠也表现出行为敏化MDMA的挑战，在成年和增强MDMA诱导的透析液DA的增加，在NAc核心，但不是在NAc壳。此外，MDMA处理的大鼠在识别记忆中表现出缺陷。咖啡因联合给药不影响上述结果。我们的研究结果表明，青少年暴露的大鼠低剂量的MDMA诱导DA神经元的神经毒性作用的DA神经元和提示相同的神经元变性的指示持久和广泛的减少。(C)2017爱思唯尔有限公司版权所有
Although MDMA (3,4-methylendioxymethamphetamine, ecstasy) neurotoxicity in serotonin neurons is largely recognized in a wide variety of species including man, neurotoxicity in dopamine (DA) neurons is thought to be species-specific. MDMA is mainly consumed by adolescents, often in conjunction with caffeine (Energy Drinks) and this association has been reported to exacerbate MDMA toxic effects. In order to model these aspects of MDMA use, vis-a-vis their impact on DA neurons, we investigated the effects of adolescent exposure to low doses of MDMA (5 mg/kg for 10 days), alone or in combination with caffeine (10 mg/kg) on neuronal and functional DA indices and on recognition memory in adult rats. MDMA reduced density of tyrosine hydroxylase (TH) positive neurons in the ventral tegmental area and in the substantia nigra pars compacta, and immunoreactivity of TH and DA transporter in the nucleus accumbens (NAc) shell and core, and caudate-putamen. This same treatment caused a reduction of basal dialysate DA in the NAc core. MDMA-pretreated rats also showed behavioral sensitization to a MDMA challenge at adulthood and potentiation of MDMA-induced increase of dialysate DA in the NAc core, but not in the NAc shell. In addition, MDMA-treated rats displayed a deficit in recognition memory. Caffeine co-administration did not affect the above outcomes. Our results show that adolescent exposure of rats to low doses of MDMA induces long-lasting and widespread reduction of DA neurons indicative of a neurotoxic effect on DA neurons and suggestive of a degeneration of the same neurons. (C) 2017 Elsevier Ltd. All rights reserved.