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Drug-related deaths in Budapest and the neurobiology of heroin abuse.

机译：布达佩斯与毒品有关的死亡和海洛因滥用的神经生物学。

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摘要

Heroin abuse is a widespread phenomenon which in Hungary, just as in other parts of the world, has been slowly but gradually increasing in the past 15 years. Our work was aimed at characterizing the population of drug-related death cases, with a special emphasis on the demographic and toxicological evaluation of the subjects. We analyzed 309 drug related death cases registered between 1994 and 2006 at the Department of Forensic Medicine at Semmelweis University, Budapest. We found that the number of drug-related deaths is slowly but constantly increasing; the majority of drug-related deaths were caused by accidental heroin overdoses whose victims were usually male, aged between 20-30 years of age, with an approximately 3.5 years of drug-use history, almost all Hungarian citizens. We also analyzed the prevalence of some infectious diseases within the population; HIV was very rare (1 case during 6 years) while hepatitis C and B and syphilis had a prevalence of 23%, 7% and 7% respectively.;In a subpopulation of the heroin overdose and control cases we collected human brain samples for further scientific assessment. In our attempt to understand the neurobiology of human heroin abuse, we examined the major brain regions linked to the "reward pathway": the ventral tegmental area (VTA) in the midbrain and the nucleus accumbens (Nacc) within the striatum. The systems most implicated in the neurobiology of heroin abuse are the dopaminergic and opioid systems; for this reasons we examined the major markers of these within the midbrain and the striatum.;As a result of our experiments, a consistent alteration of the VTA paranigral nucleus (PN) subdivision was revealed for most of the DAergic markers which strongly suggests that there is a more profound disturbance of the mesolimbic reward circuit in heroin-dependent individuals. The paralleled disturbance of dopamine transporter (DAT) mRNA and protein levels in the PN and Nacc, respectively, emphasizes the continuum of disturbances throughout the mesolimbic circuit.;In our population of subjects, 90% of individuals with an A118G polymorphism of the mu opioid receptor gene (OPMR1) were heroin abusers. Down-regulation of opioid neuropeptide genes detected in the heroin users were exaggerated in 118G subjects and were most prominent for preproenkephalin in the Nacc shell. Reduced opioid neuropeptide transcription was accompanied by increased dynorphin and enkephalin peptide concentrations exclusively in 118G heroin subjects, suggesting that the peptide processing is associated with the OPRM1 genotype. Overall, the findings from these studies emphasize a prominent mesolimbic disturbance in the brain of heroin abusers.
机译：海洛因滥用是一种普遍现象，在匈牙利，与世界其他地区一样，在过去15年中，这种现象正在缓慢但逐渐增加。我们的工作旨在表征与毒品有关的死亡病例的人群，并特别强调受试者的人口统计学和毒理学评估。我们分析了1994年至2006年间在布达佩斯Semmelweis大学法医系注册的309例与毒品有关的死亡病例。我们发现与毒品有关的死亡人数正在缓慢但不断增加。绝大多数与毒品有关的死亡是由于意外海洛因过量服用造成的，其受害者通常是男性，年龄在20-30岁之间，有大约3.5年的吸毒史，几乎是所有匈牙利公民。我们还分析了人群中某些传染病的患病率； HIV非常罕见（6年内1例），而丙型和乙型肝炎和梅毒的患病率分别为23％，7％和7％.;在海洛因过量和控制病例的亚人群中，我们收集了人脑样本以进一步科学评估。为了理解人类滥用海洛因的神经生物学，我们检查了与“奖励途径”相关的主要大脑区域：中脑腹侧被盖区（VTA）和纹状体内伏伏核（Nacc）。海洛因滥用的神经生物学中涉及最多的系统是多巴胺能和阿片样物质系统。出于这个原因，我们检查了中脑和纹状体中的这些主要标志物。；作为我们实验的结果，大多数DAergic标志物揭示了VTA旁核（PN）细分的一致变化，这强烈表明是海洛因依赖型个体中边缘性奖励回路的更深层干扰。 PN和Nacc中多巴胺转运蛋白（DAT）mRNA和蛋白水平的平行扰动分别强调了整个中边缘循环的扰动的连续性;在我们的受试者人群中，有90％的人具有mu阿片样物质的A118G多态性受体基因（OPMR1）是海洛因滥用者。在118G受试者中，海洛因使用者中检测到的阿片类神经肽基因的下调被夸大了，并且在Nacc外壳中对于前脑啡肽最为突出。仅在118G海洛因受试者中，阿片类神经肽的转录减少伴随着强啡肽和脑啡肽浓度的增加，提示该肽的加工与OPRM1基因型有关。总体而言，这些研究的结果强调了海洛因滥用者大脑中明显的中脑边缘性障碍。

著录项

  • 作者

    Horvath, Monika Csilla.;

  • 作者单位

    Semmelweis Egyetem (Hungary).;

  • 授予单位 Semmelweis Egyetem (Hungary).;
  • 学科 Biology Neuroscience.;Health Sciences Pathology.
  • 学位 Dr.
  • 年度 2007
  • 页码 136 p.
  • 总页数 136
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 神经科学;病理学;
  • 关键词

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