of behavioral stress and increased cortisol can transiently block memory retrieval (van Stegeren, 2009), with retrieval of emotional memory more strongly affected than that of neutral memory. Potential effects on emotionally charged memory and habit learning may be particularly relevant in the addictive process. Furthermore, both behavioral stress and alcohol exposure can enhance glucocorticoid-induced priming of inflammatory responses (Ellis, 1966; Frank et al., 2010). Behavioral stress and alcohol exposure also mediate inflammation via other common mechanisms. For example, stress increases gut/intestinal permeability and allows toxins to leak from the gut lumen (Garate et al., 2013). Alcohol also contributes to “leaky gut,” allowing bacterial toxins to enter the bloodstream (Adachi et al., 1995), which activates innate immune and inflammatory signaling via peripheral and central processes (Mayfield et al., 2013). Exposure to alcohol and stress may alter similar genes and inflammatory pathways that collectively contribute to the development and/or progression of AUD. Therefore, stress-induced signaling (both on the cellular and behavioral level) could play a key role in the negative affect component of withdrawal. Neuroplastic changes in CRH and glucocorticoid receptors could also participate in the enhanced sensitivity to stressors that drive relapse behavior (Koob and Volkow, 2010; Volkow et al., 2016).
