a delayed DA increase was observed at the end of the ethanol access period (Doyon et al., 2006). Conversely, KOR activation has been shown to attenuate ethanol-induced DA release in the nucleus accumbens (Lindholm et al., 2007). The same report also demonstrated that nor-BNI increased extracellular DA in the nucleus accumbens of ethanol-treated rats, but not their saline-treated counterparts (Lindholm et al., 2007). More recent reports have shown a similar increase in sensitivity to KOR manipulation in subjects exposed to chronic ethanol. Specifically, chronic ethanol exposure and withdrawal in rodents (Rose et al., 2016; Karkhanis et al., 2016a) and monkeys (Siciliano et al., 2015) resulted in enhanced sensitivity of KORs in the nucleus accumbens. These studies demonstrated increased KOR agonist-induced suppression of DA transmission using fast scan cyclic voltammetry. This hypodopaminergic state is purported to contribute to dysphoria/negative affect associated with dependence and withdrawal, which may ultimately promote elevated ethanol consumption (Siciliano et al., 2015; Rose et al., 2016; Karkhanis et al., 2016a). A recent study using an optogenetic approach showed that activation of subpopulations of dynorphin neurons in the nucleus accumbens mediate aversion (ventral shell region) and reward (dorsal shell region) (Al-Hasani et al., 2015). It will be important
