The fundamental basis of addiction is learning which is mediated by neuroplasticity. Treatment of addiction usually begins with detoxification. The signs and symptoms of withdrawal are usually opposite to the changes produced by the acute effects of the drug, appearing as a kind of rebound. The first treatment to use cross-tolerance as a maintenance strategy was discovered in heroin addiction by Vincent Dole and colleagues in the early 1960s. Researchers have been working for decades to learn the mechanism of action of important medications such as opioids. Another approach to the treatment of opioid addiction developed in preclinical laboratories involves the use of partial opioid agonists. The next advance in the treatment of tobacco dependence was the serendipitous discovery that the antidepressant bupropion reduced craving for cigarettes and improved abstinence rates. The clinical effects are analogous to the effects of buprenorphine in opioid addicts.