The Psychoactive Designer Drug and Bath Salt Constituent MDPV Causes Widespread Disruption of Brain Functional Connectivity
The Psychoactive Designer Drug and Bath Salt Constituent MDPV Causes Widespread Disruption of Brain Functional Connectivity
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DOI：
10.1038/npp.2016.40
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发表时间：
2016-08-01
影响因子：
7.6
通讯作者：
Febo, Marcelo
中科院分区：
文献类型：
--
作者：
Colon-Perez, Luis M.;Tran, Kelvin;Febo, Marcelo
“浴盐”的滥用引起了人们的关注，因为它们的不良影响，包括谵妄，暴力行为，严重的情况下还有自杀念头。浴盐成分3，4-亚甲基二氧基吡咯戊酮（MDPV）与这些和其他不良反应密切相关。急性高剂量MDPV摄入所产生的异常行为模式表明大脑区域之间的神经通信可能会中断。因此，我们确定MDPV是否对大脑功能连接产生破坏性影响，特别是在前额叶皮层区域。雄性大鼠单次给予MDPV（0.3、1.0或3.0 mg/kg）或生理盐水后进行成像。在4.7T获得静息状态脑血氧水平依赖（BOLD）图像。为了确定多巴胺传递在MDPV诱导的功能连接变化中的作用，一组大鼠在MDPV前30分钟接受多巴胺D-1/D-2受体拮抗剂顺式氟喷噻吨（0.5 mg/kg）。MDPV剂量依赖性地降低了功能连接。对其影响的详细分析显示，额叶皮质和纹状体区域之间的连通性降低。这包括前边缘前额叶皮层与额叶皮层其他区域之间的连接，以及岛叶皮层与下丘脑、腹侧和背侧纹状体区域之间的连接。虽然连接性的降低似乎很普遍，但这些区域与躯体感觉皮层之间的连接性并没有受到严重影响。多巴胺受体阻断剂并不能阻止MDPV诱导的功能连接减少。这些结果为MDPV的体内作用机制提供了新的特征。据报道，患有精神病的患者的脑功能连接性降低，并且与认知功能障碍、视听幻觉和负面情感状态有关，类似于MDPV诱导的中毒所报告的那些。目前的研究结果表明，涉及额叶皮层和纹状体区域的功能连接网络的中断可能有助于MDPV的不良影响。
The abuse of 'bath salts' has raised concerns because of their adverse effects, which include delirium, violent behavior, and suicide ideation in severe cases. The bath salt constituent 3,4-methylenedioxypyrovalerone (MDPV) has been closely linked to these and other adverse effects. The abnormal behavioral pattern produced by acute high-dose MDPV intake suggests possible disruptions of neural communication between brain regions. Therefore, we determined if MDPV exerts disruptive effects on brain functional connectivity, particularly in areas of the prefrontal cortex. Male rats were imaged following administration of a single dose of MDPV (0.3, 1.0, or 3.0 mg/kg) or saline. Resting state brain blood oxygenation level-dependent (BOLD) images were acquired at 4.7 T. To determine the role of dopamine transmission in MDPV-induced changes in functional connectivity, a group of rats received the dopamine D-1/D-2 receptor antagonist cis-flupenthixol (0.5 mg/kg) 30 min before MDPV. MDPV dose-dependently reduced functional connectivity. Detailed analysis of its effects revealed that connectivity between frontal cortical and striatal areas was reduced. This included connectivity between the prelimbic prefrontal cortex and other areas of the frontal cortex and the insular cortex with hypothalamic, ventral, and dorsal striatal areas. Although the reduced connectivity appeared widespread, connectivity between these regions and somatosensory cortex was not as severely affected. Dopamine receptor blockade did not prevent the MDPV-induced decrease in functional connectivity. The results provide a novel signature of MDPV's in vivo mechanism of action. Reduced brain functional connectivity has been reported in patients suffering from psychosis and has been linked to cognitive dysfunction, audiovisual hallucinations, and negative affective states akin to those reported for MDPV-induced intoxication. The present results suggest that disruption of functional connectivity networks involving frontal cortical and striatal regions could contribute to the adverse effects of MDPV.