John Kramer1, Danielle M Dick2,3, Andrea King4, Lara A Ray5, Kenneth J Sher6, Ashley Vena4, Leandro F Vendruscolo7, Laura Acion1,8. 1. Department of Psychiatry, University of Iowa Carver College of Medicine, 200 Hawkins Dr, 1882JPP, Iowa City, IA 52242-1009, USA. 2. Department of Psychology, Virginia Commonwealth University, 612 N. Lombardy St., Richmond, VA 23284, USA. 3. Department Human and Molecular Genetics, Virginia Commonwealth University, 806 West Franklin Street, Box 842018, Richmond, VA 23284, USA. 4. Department of Psychiatry and Behavioral Neuroscience, University of Chicago, 5841 S. Maryland Ave., Room L470, Chicago, IL 60637, USA. 5. Department of Psychology, UCLA, 1285 Franz Hall, Los Angeles, CA 90095, USA. 6. Department of Psychological Sciences, University of Missouri, 210 McAlester Hall, Columbia, MO 65211, USA. 7. Neurobiology of Addiction Section, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD 21224, USA. 8. Instituto de Cálculo, Universidad de Buenos Aires-CONICET, Intendente Güiraldes 2160, C1428EGA, Buenos Aires, Argentina.
Abstract
AIM: The purpose of this brief narrative review is to address the complexities and benefits of extending animal alcohol addiction research to the human domain, emphasizing Allostasis and Incentive Sensitization, two models that inform many pre-clinical and clinical studies. METHODS: The work reviewed includes a range of approaches, including: a) animal and human studies that target the biology of craving and compulsive consumption; b) human investigations that utilize alcohol self-administration and alcohol challenge paradigms, in some cases across 10 years; c) questionnaires that document changes in the positive and negative reinforcing effects of alcohol with increasing severity of addiction; and d) genomic structural equation modeling based on data from animal and human studies. RESULTS: Several general themes emerge from specific study findings. First, positive reinforcement is characteristic of early stage addiction and sometimes diminishes with increasing severity, consistent with both Allostasis and Incentive Sensitization. Second, evidence is less consistent for the predominance of negative reinforcement in later stages of addiction, a key tenant of Allostasis. Finally, there are important individual differences in motivation to drink at a given point in time as well as person-specific change patterns across time. CONCLUSIONS: Key constructs of addiction, like stage and reinforcement, are by necessity operationalized differently in animal and human studies. Similarly, testing the validity of addiction models requires different strategies by the two research domains. Although such differences are challenging, they are not insurmountable, and there is much to be gained in understanding and treating addiction by combining pre-clinical and clinical approaches.
AIM: The purpose of this brief narrative review is to address the complexities and benefits of extending animal alcohol addiction research to the human domain, emphasizing Allostasis and Incentive Sensitization, two models that inform many pre-clinical and clinical studies. METHODS: The work reviewed includes a range of approaches, including: a) animal and human studies that target the biology of craving and compulsive consumption; b) human investigations that utilize alcohol self-administration and alcohol challenge paradigms, in some cases across 10 years; c) questionnaires that document changes in the positive and negative reinforcing effects of alcohol with increasing severity of addiction; and d) genomic structural equation modeling based on data from animal and human studies. RESULTS: Several general themes emerge from specific study findings. First, positive reinforcement is characteristic of early stage addiction and sometimes diminishes with increasing severity, consistent with both Allostasis and Incentive Sensitization. Second, evidence is less consistent for the predominance of negative reinforcement in later stages of addiction, a key tenant of Allostasis. Finally, there are important individual differences in motivation to drink at a given point in time as well as person-specific change patterns across time. CONCLUSIONS: Key constructs of addiction, like stage and reinforcement, are by necessity operationalized differently in animal and human studies. Similarly, testing the validity of addiction models requires different strategies by the two research domains. Although such differences are challenging, they are not insurmountable, and there is much to be gained in understanding and treating addiction by combining pre-clinical and clinical approaches.
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