Our data may also complement the literature examining the role of endogenous opiates in the reinforcing effects of alcohol. Recent imaging data have supported that alcohol induces endogenous opioid release in the nucleus accumbens (Mitchell et al., 2012), a target of the mesolimbic dopamine projection from the ventral tegmental area. Some pre-clinical studies, however, suggest that some of the reinforcing effects of alcohol may in fact be independent of this dopamine pathway and are better explained by opioidergic effects in this system. Specifically, after toxic lesion of the mesolimbic dopamine pathway, rats are able to acquire and continue to seek ethanol in an operant paradigm (Koistinen et al., 2001, Shoemaker et al., 2002). When delivered systemically, naloxone (Shoemaker et al., 2002), an opioid antagonist with high affinity for the mu receptor, and naltrexone (Koistinen et al., 2001), reduce this voluntary drinking in rats with dopaminergic damage. However, mice lacking D2 receptors do show reduced preference for ethanol as well (Phillips et al., 1998), indicating that dopamine binding at these sites remains an important component in ethanol self-administration behavior.
