– Pituitary adenylate cyclase activating polypeptide (PACAP, Adcyap1) activation of PAC1 receptors ( Adcyap1r1) significantly increases excitability of guinea pig cardiac neurons. This modulation of excitability is mediated in part by plasma membrane G protein-dependent activation of adenylyl cyclase and downstream signaling cascades. Studies point to the potential role of the (pituitary) adenylate cyclase activating polypeptide receptor 1 (ADCYAP1R1) gene, which has been implicated in stress response, in posttraumatic stress disorder (PTSD). Pituitary adenylate cyclase-activating polypeptide (PACAP; Adcyap1) and its cognate PAC1 receptor (Adcyap1r1) are expressed in peripheral nociceptive pathways, participate in anxiety-related responses and have been have been linked to posttraumatic stress disorder and other mental health afflictions. Recent studies revealed the role of the PAC1 (ADCYAP1R1) gene variability in vulnerability to posttraumatic stress disorder in women. Due to the relatively high comorbidity of posttraumatic stress disorder and substance use disorder, we hypothesized about possible associations between PAC1 gene and problematic alcohol use.