HTR1A encodes the 5-hydroxytryptamine (Serotonin) receptor 1A subunit, a G protein-coupled receptor that mediates the actions of serotonin in the brain (Fig. 1 and Table 3). Rodent animal models and human clinical studies suggest dysfunction in serotonin (5-HT) innervation and transmission in early-onset genetically determined or type 2 alcoholism. A candidate gene association study found an association with variants of HTR1A with suicide attempts in alcohol dependent patients (Wrzosek et al., 2011). A 5HT1A/B antagonist (WAY100635) reduces drug seeking during initial abstinence in rats (Kohtz and Aston-Jones, 2017). In addition, serotonin specific neuronal reduction in expression of Htr1A in mice contributes to cocaine seeking behavior and inhibition of dorsal raphe 5-HT1A autoreceptors attenuates cocaine self-administration in rats with prolonged extended access, but not 1 h access to the drug (You et al., 2016). Finally, a quantitative trait gene, the multiple PDZ domain protein (MPDZ), mediates drug withdrawal responses in mice and humans (Shirley et al., 2004; Fehr et al., 2002; Reilly et al., 2008; Milner et al., 2015; Chen and Buck, 2010; Chen et al., 2011). MPDZ is critical for
