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.