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，他们的家庭和社区的不利影响有关。它是一种慢性复发性疾病，很少有有效的预防和治疗策略。此外，为什么一个人开始和保持海洛因服用仍然不清楚。压力和负面情绪对海洛因的使用有很大的影响。压力可能会驱使一些人开始使用海洛因，压力增加了海洛因的愉悦效果，压力增加了海洛因戒断的厌恶效果。这些影响将鼓励成瘾，并阻止成瘾者寻求治疗。压力也可能导致一个原本没有吸毒的人重新陷入海洛因成瘾，尽管他已经有一段时间没有吸毒了。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。我们将检验一个假设，即海洛因的使用实际上会对大脑中控制压力反应的神经网络产生深刻的改变。该项目使用一种简单的海洛因成瘾动物模型，即给大鼠注射吗啡，以研究对应激反应至关重要的几种基因的调节。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，心血管和行为对压力的反应。该项目将确定在海洛因成瘾期间改变的大脑部分，并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，该项目将帮助我们确定治疗干预（心理和药理）的目标，并可能破坏成瘾循环。

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.