instance, alcohol use leads to the release of endogenous opioids, which activate mu-opioid receptors on GABAergic interneurons in the ventral tegmental area, resulting in attenuation of inhibitory tone from these onto mesolimbic dopamine-neurons, and ultimately increased dopamine release in the nucleus accumbens. Over time, chronic alcohol use eventually leads to a hypodopaminergic state that becomes the driving force behind continued alcohol and/or other drug seeking behaviors (Volkow et al., 2007). To date, genetic studies of AD have highlighted polymorphisms in the genes for GABA (e.g., GABRA2; Dick et al., 2006a; 2006b; Edenberg et al., 2004; Fehr et al., 2006; Ittiwut et al., 2011; Lind et al., 2008a; Lydall et al., 2011; Matthews et al., 2007; Philibert et al., 2009), dopamine (e.g., DRD4; Connor et al., 2007; Dick et al., 2007; Park et al., 2011; Pinto et al., 2009; Yang et al., 2008), serotonin (e.g., SLC6A4; McHugh et al., 2010; Philibert et al., 2008), and opioid receptors (e.g., OPRM1; Chen et al., 2011a), and the dopamine enzyme, catechol-O-methyl-transferase (COMT; He et al., 2008) among others.
