Mu-opioid receptor desensitization in ventral tegmental neurones: cellular mechanisms and functional consequences

阿片类药物，如吗啡和海洛因被广泛滥用，在英国约有27万问题阿片类药物使用者。当有人持续使用阿片类药物一段时间时，他们会对其影响产生耐受性，并需要使用更多来获得？高？他们最初经历的，并避免退出。这种容忍的过程助长了鸦片成瘾所固有的健康和社会问题。到目前为止，吗啡耐受性发展的潜在机制仍不清楚。在这个建议中，我们将调查阿片类药物的耐受性在一个单一的细胞水平上，以调查潜在的细胞内信号转导机制，可能是阿片类药物耐受性的发展。然后，我们将继续研究如何干扰这些信号传导机制可以影响阿片类药物耐受性的发展。只有了解吗啡耐受如何在细胞水平上发生，我们才能开始设计更好的治疗阿片类药物滥用的未来。

Opiate drugs such as morphine and heroin are widely abused, with approximately 270,000 problem opiate users in the UK. When somebody uses opiates consistently for a while, they become tolerant to its effects and need to use more to get the ?high? they initially experienced and to stave off withdrawal. This process of tolerance contributes to the health and social problems inherent in opiate addiction. To date the mechanism(s) underlying the development of morphine tolerance remain unknown. In this proposal we will investigate opiate tolerance on a single cellular level, in order to investigate potential intracellular signalling mechanisms that may underlie the development of opiate tolerance. We will then go on to study how interfering with these signalling mechanisms can affect the development of opiate tolerance. It is only by understanding how morphine tolerance occurs on a cellular level that we can begin to design better treatments for opiate abuse in the future.