that often lasts for years. Studies in iMOs are often just the opposite. Genetic variance in iMOs is usually generated in the laboratory, although naturally occurring genetic variation in EtOH responsiveness in worms and flies has been assessed in some studies (Davies et al., 2004a; Morozova et al., 2009). Most studies in iMOs have used genetic manipulations that are the most severe that still allow the organism to live and perform basic tasks like locomotion, and—since they are maintained in a laboratory setting—these genetic manipulations largely escape the forces of evolution. Alcohol exposure in iMOs is also typically acute (lasting minutes to hours). The alcohol-related behaviors routinely assessed in iMOs (sedation, tolerance, locomotor activation) are fundamentally distinct from and simpler than the phenotypes analyzed in humans (alcohol abuse, alcohol dependence, alcohol craving, etc.) because iMO phenotypic end points are devoid of human social influences and occur in response to forced exposure to alcohol. Consequently, the experimental questions that are addressed in iMOs and humans are substantially different. Studies in humans typically address questions such as: What are the naturally occurring genetic variants that are associated with an AUD, or an endophenotype of an AUD, in response to chronic, voluntary alcohol
