Although much of the early research with animal models focused on the acute rewarding effects of drugs of abuse, focus is shifting to the study of chronic drug administration-induced brain changes that decrease the threshold for relapse, which corresponds more closely to human imaging studies of individuals who have substance use disorders. One of the main goals of neurobiological research is to understand changes at the molecular, cellular, and neurocircuitry levels that mediate the transition from occasional, controlled substance use to loss of control in drug intake and chronic addiction.2 Because only some substance users make this transition, neurobiological factors that influence the diverse individual differences in drug responses have also attracted increasing interest. Cogent arguments have been made that addictions are similar to other chronic relapsing disorders—with individual differences in responses to the same exogenous challenges and limited effi cacy of treatment—such as diabetes, asthma, and hypertension.3
