Age as a factor in stress and alcohol interactions: A critical role for the kappa opioid system

The endogenous kappa opioid system has primarily been shown to be involved with a state of dysphoria and aversion. Stress and exposure to drugs of abuse, particularly alcohol, can produce similar states of unease and anxiety, implicating the kappa opioid system as a target of stress and alcohol. Numerous behavioral studies have demonstrated reduced sensitivity to manipulations of the kappa opioid system in early life relative to adulthood, and recent reports have shown that the kappa opioid system is functionally different across ontogeny. Given the global rise in early-life stress and alcohol consumption, understanding how the kappa opioid system responds and adapts to stress and/or alcohol exposure differently in early life and adulthood is imperative. Therefore, the objective of this review is to highlight and discuss studies examining the impact of early-life stress and/or alcohol on the kappa opioid system, with focus on the documented neuroadaptations that may contribute to future vulnerability to stress and/or increase the risk of relapse. We first provide a brief summary of the importance of studying the effects of stress and alcohol during early life (prenatal, neonatal/juvenile, and adolescence). We then discuss the literature on the effects of stress or alcohol during early life and adulthood on the kappa opioid system. Finally, we discuss the few studies that have shown interactions between stress and alcohol on the kappa opioid system and provide some discussion about the need for studies investigating the development of the kappa opioid system.