Drugs of abuse activate brain reward systems, and research on drug addiction has in large part defined the neurocircuitry of reward. This line of investigation is fundamental because changes to how the drug-induced reward system is activated are key to the understanding of the development of addiction.4 Reward is defined herein as any event that increases the probability of a response with a positive hedonic component. A principal focus of research on the neurobiology of the rewarding effects of abused drugs has been the origins and terminal areas of the ascending mesocorticostriatal dopamine systems that have a key role in the rewarding properties of nearly all drugs of abuse (table 1).34 In humans, positron emission tomography studies have shown that intoxicating doses of alcohol and drugs release dopamine and opioid peptides into the ventral striatum,16,35 and that fast and steep release of dopamine is associated with the subjective sensation of the so-called high.36 This is because fast and steep increases in dopamine activate low-affi nity dopamine D1 receptors, which are necessary for the rewarding effects of drugs37 and for triggering
