Alcohol produces euphoria, among many other effects, and acts on several molecular targets in the brain. A recent analysis of 37 KO mouse lines has provided evidence that alcohol consumption is controlled by multiple physiological systems (Blednov et al., 2012). Among these, endogenous opioids represent an important neurobiological component of alcohol intake and dependence (Gianoulakis, 2009; Koob et al., 2003). Extensive research has implicated endogenous opioid peptide release in alcohol consumption, and naltrexone, a general opioid antagonist, showed some efficacy in the treatment of alcoholism (Koob et al., 2009). Knockout mice have provided key insights into opioid mechanisms underlying alcohol-related behaviors (see Table 5). Mice lacking mu opioid receptors did not self-administer alcohol under several conditions, including oral self-administration and the two-bottle choice, and did not display conditioned place preference to alcohol (Becker et al., 2002; Hall et al., 2001; Roberts et al., 2000), demonstrating that mu receptors are essential to consumption and motivation for alcohol. Mu receptor also plays a role in alcohol withdrawal as the absence of mu receptor accelerated the progression of physical signs of withdrawal (Ghozland
