Addiction is defined as compulsive drug use despite negative consequences. The goals of the addicted person become narrowed to obtaining, using, and recovering from drugs, despite failure in life roles, medical illness, risk of incarceration, and other problems. An important char- acteristic of addiction is its stubborn persistence (1, 2). Al- though some individuals can stop compulsive use of to- bacco, alcohol, or illegal drugs on their own, for a large number of individuals rendered vulnerable by both ge- netic and nongenetic factors (3–5), addiction proves to be a recalcitrant, chronic, and relapsing condition (2). The central problem in the treatment of addiction is that even after prolonged drug-free periods, well after the last with- drawal symptom has receded, the risk of relapse, often precipitated by drug-associated cues, remains very high (6, 7). Were this not the case, treatment could simply con- sist of locking addicted people away in a protective envi- ronment until withdrawal symptoms were comfortably behind them, issuing a stern warning about future behav- ior, and having done with it.
Memory disorders are often thought of as conditions in- volving memory loss, but what if the brain remembers too much or too powerfully records pathological associations? During the last decade, advances in understanding the role of dopamine in reward-related learning (8) have made a compelling case for a “pathological learning” model of addiction that is consistent with long-standing observa- tions about the behavior of addicted people (6). This work, along with more recent computational analyses of dopa- mine action (9, 10), has suggested mechanisms by which drugs and drug-associated stimuli might attain their moti- vational power.