Molecular Mechanisms Underlying Opiate Addiction: Implications for Medications Development

Progress is being made in identifying molecular and cellular adaptations induced in specific brain regions by long-term opiate exposure and in relating these adaptations to specific aspects of opiate addiction. In the locus coeruleus, the major noradrenergic nucleus in brain which plays an important role in physical opiate dependence and withdrawal, upregulation of the cAMP pathway in response to chronic opiate administration has been shown to be one important mechanism involved. In the mesolimbic dopamine system, which plays an important role in the reinforcing effects of opiates after short- and long-term exposure, some similar and some different types of opiate-induced adaptations have been identified. As an increasingly complete understanding of opiate action is obtained, this knowledge will provide the framework for the development of novel therapeutic agents to treat opiate addiction.