Stress has been implicated as a risk factor in vulnerability to the initiation and maintenance of opiate abuse and is thought to play an important role in relapse in subjects with a history of abuse. Conversely, chronic opiate use and withdrawal are stressors and can potentially predispose individuals to stress-related psychiatric disorders. Because the interaction of opiates with stress response systems has potentially widespread clinical consequences, it is important to delineate how specific substrates of the stress response and endogenous opioid systems interact and the specific points at which stress circuits and endogenous opioid systems intersect. The purpose of this review is to present and discuss the results of studies that have unveiled the complex circuitry by which stress-related neuropeptides and endogenous opioids coregulate activity of the locus coeruleus (LC)-norepinephrine (NE) system and how chronic morphine, or stress, disturbs this regulation. © 2013 Elsevier Inc.
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