Several AUD risk models have been proposed based on the subjective response to alcohol, each derived using oral alcohol challenges and suggesting a relationship between alcohol pharmacokinetics and pharmacodynamics. The two models with the most support are the low level of response model and the differentiator model. The low level of response model is based on the finding that males with a positive family history of AUD (FHP) reported lesser subjective responses to an alcohol challenge than those without family history (family history negative, FHN). 15 The differentiator model posits that FHP individuals are more sensitive to the rewarding effects on the ascending limb (period of increasing BrAC), and more tolerant to the sedating effects on the descending limb (when BrAC is decreasing), compared with FHN controls. 16 Ingestion of alcohol, however, results in substantial variation in peak BrAC and latency to peak BrAC, limiting experimental control over how quickly alcohol exposures change (e.g., Norberg et al. 17 and Ramchandani et al. 18 ). Consequently, most research has focused on the response to alcohol on the ascending versus descending limbs.
