As has been hypothesized in humans, and now demonstrated convincingly in animal studies, stress is one of the key factors in facilitating reward associated with initial drug exposure. In addition, stress increases drug craving and relapse back into drug seeking. Studies have demonstrated a positive correlation of stress and drug craving in humans (114
), indicating an activation of reward pathways following exposure to a stressor (115
). A significant gap in our understanding of addiction is whether alterations in brain chemistry observed in chronic addicts is caused by environmental factors, such as physical or sexual abuse, which are known to lead to illicit drug use, or by the long-term drug use itself. Recently, it was demonstrated that humans with self-reported increased life stress display increased drug reward to an acute injection of amphetamine (116
), further supporting the hypothesis that exposure to a chronic stress environment increases the risk of developing addictive behavior. Furthermore, the high-stress group exhibited a decrease in dopamine release at baseline as well as in response to amphetamine (116
), indicating that this decreased dopamine response might constitute a vulnerability to addiction. In a monkey model of social hierarchy, the amount or availability of dopamine D2 receptors was increased in dominant monkeys, whereas no change was observed in subordinate cage mates (117
). Interestingly, cocaine was more reinforcing in the subordinate than in the dominant monkeys (117
), indicating that environmental modifications of the dopamine system may alter vulnerability to addiction. However, future studies examining the molecular targets and signaling pathways altered by chronic environmental, physical, and psychological stress and their effects on addictive behaviors need to be completed.
Although effective treatments for drug abuse involve both behavioral therapy and medication, the list of medications approved by the FDA for treatment of addiction is limited. Indeed, there are currently no approved medications for cocaine addiction. Furthermore, many of the treatments available are given when the addict is actively using the addictive substance. Current treatments for alcohol, nicotine, and opiate addiction are used to reduce or stop drug intake. For example, naltrexone decreases alcohol intake, allowing for a more productive lifestyle. Bupropion is prescribed in conjunction with nicotine replacement therapy when patients are still smoking. Very few treatments are prescribed during the withdrawal period, in particular to prevent relapse. Over the last 10–15 years, research into the effects of stress on the addiction cycle has identified both peripheral and central CRF systems as key players in linking stress and addiction. Although therapeutic drugs targeting this system are being examined for their treatment efficacy, additional research examining withdrawal and relapse, in particular stress-induced relapse, is needed to further determine putative therapeutic targets.