Increased vulnerability to stress during opiate dependence: Molecular, anatomical, and behavioural correlates

海洛因成瘾是澳大利亚的一个主要健康和社会问题。它始终与对个人用户、其家庭和社区的不利影响相关联。这是一种慢性复发的情况，几乎没有有效的预防和治疗策略。此外，为什么一个人会开始并坚持吸食海洛因，目前还不清楚。压力和负面情绪对海洛因的使用有很大的影响。压力可能会促使一些人开始使用海洛因，压力会增加海洛因的愉悦效果，压力会增加海洛因戒断的厌恶效果。这些影响将鼓励上瘾，并阻止成瘾者寻求治疗。压力还会导致一个原本不吸毒的人重新染上海洛因瘾，尽管他已经戒了一段时间的毒品。在这个项目中，我们将研究为什么压力对海洛因成瘾者和海洛因成瘾有如此大的影响。我们将测试这一假设，即海洛因使用实际上会导致大脑中控制压力反应的神经网络发生深刻变化。这个项目使用了一个简单的海洛因成瘾动物模型，向大鼠注射吗啡来研究几个基因的调节，这些基因在应对压力方面很重要。我们还将研究这种暴露和基因表达的变化如何改变神经生物学、心血管和行为对应激的反应。这个项目将确定在海洛因成瘾期间大脑的哪些部分发生了变化，并将确定为什么海洛因成瘾者比普通人群更容易受到压力的影响。因此，这个项目将帮助我们确定治疗干预的目标(包括心理和药物干预)，并可能扰乱成瘾循环。

Heroin addiction is a major health and societal problem in Australia. It is consistently associated with an adverse impact upon individual users, their families, and communities. It is a chronically relapsing condition for which few, if any effective prevention and treatment strategies exist. Moreover, why an individual initiates and maintains heroin taking remains unclear. Stress and negative emotions have a strong impact on heroin use. Stress may drive some individuals to start using heroin, stress increases the pleasurable effects of heroin and stress increases the aversive effects of heroin withdrawal. These effects will encourage addiction and discourage addicts from seeking treatment. Stress can also cause an otherwise drug-free individual to relapse to heroin addiction despite having been drug-free for some time. In this project we will study why stress has such a large impact on heroin addicts and heroin addiction. We will test the hypothesis that heroin use actually produces profound alterations in the neural network in the brain which controls responses to stress. This project uses a simple animal model of heroin addiction whereby rats are injected with morphine to study the regulation of several genes which are important in responding to stress. We will also study how this exposure and changes in gene expression alter neurobiological, cardiovascular, and behavioural responses to stress. This project will identify parts of the brain that are altered during heroin addiction, and will also identify why heroin addicts are more vulnerable to stress than the general population. Therefore, this project will help us to identify targets for therapeutic intervention (both psychological and pharmacological) and possibly disrupt the addictive cycle.