Molecular Mechanisms of Opioid Dependence by Using Knockout Mice

Opium, extracted from the seed of the poppy Papaver somniferum , has been used and abused for several thousand years. This substance is highly efficient to relieve pain or treat dysentery, and also shows strong euphoric and addictive properties. Due to their exceptional therapeutic potential, the active ingredients of opium have been the subject of intense investigations. Morphine, named after Morpheus, the Greek god of dreams, was isolated in 1806 (1) and is considered the prototypic opioid compound. This compound retains both analgesic and addictive properties of opium. Despite numerous adverse effects (2), morphine remains the best painkiller in contemporary medicine, and its clinical use is under tight regulation. In 1898 heroin was chemically synthesized by morphine diacetylation, in an attempt to obtain a drug with lower abuse liability. In fact, this morphine derivative showed even higher addictive potential due to its distinct pharmacokinetic properties. Heroin is being illegally abused worldwide and represents a major public health problem. Attempts to dissociate opioid analgesia from opioid addiction have been unsuccessful so far.