Several lines of evidence indicate that ethanol interferes with endogenous opioid mechanisms which are closely linked with dopamine transmission in the mesolimbic pathway (Herz 1997). Acute ethanol administration induced a transient decrease in pro-enk mRNA expression in the VTA and a prolonged increase in the NAc core and shell regions that peaked 2 h after ethanol exposure (Mendez and Morales-Mulia 2006, Chang, Barson et al. 2010). Local administration of opioid receptor antagonist naloxone in the NAc, but not the VTA (Valenta, Job et al. 2013), reduced ethanol intake (Barson, Carr et al. 2009). Using displacement of radiolabeled μ opioid receptor agonist before and immediately after ethanol consumption in humans, ethanol drinking was shown to induce opioid release in the NAc and orbitofrontal cortex (Mitchell, O'Neil et al. 2012). Further, local administration of opioid receptor antagonist in the anterior cingulate cortex disrupted expression of an ethanol-induced conditioned place preference (Gremel, Young et al. 2011).
