Addiction and the brain: The neurobiology of compulsion and its persistence

People take addictive drugs to elevate mood, but with repeated use these dr ugs produce serious unwanted effects, which can Include tolerance to some d rug effects, sensitization to others, and an adapted state - dependence - w hich sets the stage for withdrawal symptoms when drug use stops. The most s erious consequence of repetitive drug taking, however, is addiction: a pers istent state in which compulsive drug use escapes control, even when seriou s negative consequences ensue, Addiction is characterized by a long-lasting risk of relapse, which is often Initiated by exposure to drug-related cues . Substantial progress has been made in understanding the molecular and cel lular mechanisms of tolerance, dependence and withdrawal, but as yet we und erstand little of the neural substrates of compulsive drug use and its rema rkable persistence. Here we review evidence for the possibility that compul sion and its persistence are based on a pathological usurpation of molecula r mechanisms that are normally involved in memory.