“Chronic early-life stress, such as childhood neglect, often results in anxiety and affective disorders and increased probability of drug and alcohol abuse in adulthood…”


“…the mesolimbic dopamine (DA) system may have an integral role in the pathophysiology associated with childhood stress. Unfortunately, while many human and animal studies have documented profound disruptions of DA signaling associated with a wide range of chronic early-life stressors…”

“The nucleus accumbens (NAc) is known to have a critical role in motivated behaviors and reward seeking via modulation of DA levels. Additionally, the NAc is implicated in the modulation of stress and anxiety like negative affective behaviors. Kappa opioid receptors (KORs) are located presynaptically on DA terminals and suppress DA release in the NAc…Previous data suggest that exposure to chronic stress, such as repeated withdrawal from chronic intermittent ethanol (CIE) exposure, leads to prolonged activation of KORs, possibly contributing to reduced DA function, which is positively correlated with negative affect.”

Early-Life Social Isolation Stress Increases Kappa Opioid Receptor Responsiveness and Downregulates the Dopamine System
Anushree N Karkhanis, et. al. – Neuropsychopharmacology (2016), 1–12


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