Conversely, the aforementioned imaging study revealed that Asp40 carriers had greater hemodynamic response in mesocorticolimbic areas both before and after a priming dose compared to homozygotes for the Asn40 allele (Filbey et al., 2008). Thus, the pharmacological effects of alcohol on endogenous opioids in the mesolimbic system (Erickson, 1996; Herz, 1997; Kreek, 1996) may be moderated by this polymorphism. These results are relevant to the literature showing that the Asn40Asp allele moderates the effects of naltrexone (Anton et al., 2008; McGeary et al., 2006; Oslin et al., 2003; Ray & Hutchison, 2007), a pharmacotherapy thought to dampen the reinforcing effects of alcohol (King et al., 1997; Swift et al., 1994; Volpicelli et al., 1995). Additional studies and converging evidence from multiple lines of research (e.g., laboratory-based, clinical trials, EMA-based, neuroimaging) are necessary to more fully elucidate these complex mechanisms of genetic causation and their clinical implications to the etiology and treatment of alcohol use disorders.
