Human Laboratory Paradigms in Alcohol Research

Department of Psychiatry, University of Pennsylvania, Pennsylvania, USA.
Alcoholism Clinical and Experimental Research (Impact Factor: 3.21). 02/2012; 36(6):972-83. DOI: 10.1111/j.1530-0277.2011.01704.x
Source: PubMed


Human laboratory studies have a long and rich history in the field of alcoholism. Human laboratory studies have allowed for advances in alcohol research in a variety of ways, including elucidating neurobehavioral mechanisms of risk, identifying phenotypically distinct subtypes of alcohol users, investigating the candidate genes underlying experimental phenotypes for alcoholism, and testing mechanisms of action of alcoholism pharmacotherapies on clinically relevant translational phenotypes, such as persons exhibiting positive-like alcohol effects or alcohol craving. Importantly, the field of human laboratory studies in addiction has progressed rapidly over the past decade and has built upon earlier findings of alcohol's neuropharmacological effects to advancing translational research on alcoholism etiology and treatment.
To that end, the new generation of human laboratory studies has focused on applying new methodologies, further refining alcoholism phenotypes, and translating these findings to studies of alcoholism genetics, medication development, and pharmacogenetics. The combination of experimental laboratory approaches with the recent developments in neuroscience and pharmacology has been particularly fruitful in furthering our understanding of the impact of individual differences in alcoholism risk and in treatment response.
This review of the literature focuses on human laboratory studies of subjective intoxication, alcohol craving, anxiety, and behavioral economics. Each section discusses opportunities for phenotype refinement under laboratory conditions, as well as its application to translational science of alcoholism. A summary and recommendations for future research are also provided.

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Available from: Meghan E Morean, Sep 14, 2015
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    • "To that end, proof-of-concept laboratory studies offer an important bridge between preclinical findings and clinical application to treatment-seeking samples. Human laboratory models can be used to guide identification of medications with promise of efficacy by collecting both safety and alcohol/drug interaction data along with initial demonstration of subjective responses to alcohol/drug, cue-reactivity, and selfadministration models (Plebani et al., 2012). Human laboratory models can also aid in the effective translation of preclinical findings by elucidating the biobehavioral mechanisms by which pharmacotherapies may be efficacious for addiction (Ray, Hutchison, & Tartter, 2010; Ray, Mackillop, & Monti, 2010). "
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    ABSTRACT: Studies have implicated neuroinflammatory processes in the pathophysiology of various psychiatric conditions, including addictive disorders. Neuroimmune signaling represents an important and relatively poorly understood biological process in drug addiction. The objective of this review is to update the field on recent developments in neuroimmune therapies for addiction. First, we review studies of neuroinflammation in relation to alcohol and methamphetamine dependence followed by a section on neuroinflammation and accompanying neurocognitive dysfunction in HIV infection and concomitant substance abuse. Second, we provide a review of pharmacotherapies with neuroimmune properties and their potential development for the treatment of addictions. Pharmacotherapies covered in this review include ibudilast, minocycline, doxycycline, topiramate, indomethacin, rolipram, anakinra (IL-1Ra), peroxisome proliferator-activated receptor agonists, naltrexone, and naloxone. Lastly, summary and future directions are provided with recommendations for how to efficiently translate preclinical findings into clinical studies that can ultimately lead to novel and more effective pharmacotherapies for addiction.
    Full-text · Article · Sep 2014 · International Review of Neurobiology
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    • "Understanding whether different triggers for craving probe different underlying mechanisms is important for treating a disease as heterogeneous as AD. Moreover, although laboratory methodologies related to alcohol research are well-characterized (Plebani et al. 2012), there are few studies comparing these paradigms. The current study addresses this gap by comparing two methods using both stress and alcohol cues to induce craving, making an important contribution to our understanding of the mechanisms underlying craving for alcohol. "
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    ABSTRACT: Alcohol addiction is a chronic relapsing disorder that presents a substantial public health problem, and is frequently co-morbid with posttraumatic stress disorder (PTSD). Craving for alcohol is a predictor of relapse to alcohol use, and is triggered by cues associated with alcohol and trauma. Identification of reliable and valid laboratory methods for craving induction is an important objective for alcoholism and PTSD research. The present study compares two methods for induction of craving via stress and alcohol cues in individuals with co-morbid alcohol dependence (AD) and PTSD: the combined Trier social stress test and cue reactivity paradigm (Trier/CR), and a guided imagery (Scripts) paradigm. Outcomes include self-reported measures of craving, stress and anxiety as well as endocrine measures. Subjects were 52 individuals diagnosed with co-morbid AD and PTSD seeking treatment at the National Institute on Alcohol Abuse and Alcoholism inpatient research facility. They participated in a 4-week inpatient study of the efficacy of a neurokinin 1 antagonist to treat co-morbid AD and PTSD, and which included the two challenge procedures. Both the Trier/CR and Scripts induced craving for alcohol, as well as elevated levels of subjective distress and anxiety. The Trier/CR yielded significant increases in adrenocorticotropic hormone and cortisol, while the Scripts did not. Both paradigms are effective laboratory means of inducing craving for alcohol. Further research is warranted to better understand the mechanisms behind craving induced by stress versus alcohol cues, as well as to understand the impact of co-morbid PTSD and AD on craving.
    Full-text · Article · Jun 2014 · Addiction Biology
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    • "Alcohol craving is also measured in the human laboratory during alcohol administration, or alcohol challenges, alongside the measurement of subjective responses to alcohol (Plebani et al., 2012; Ray et al., 2010a). Whereas experimental methods have been developed and validated to assess alcohol craving under controlled conditions, self-reports are also needed, particularly in the context of large-scale studies where experimental paradigms may be impractical. "
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    ABSTRACT: Objective: The abbreviated Desires for Alcohol Questionnaire (DAQ) is a self-report assessment of craving comprising the following subscales: (a) strong desires/intentions to drink, (b) negative reinforcement, and (c) positive reinforcement and ability to control drinking. Although the DAQ is sensitive to changes in alcohol craving precipitated by alcohol administration and/or cue exposure, no studies to date have examined the relationship between DAQ scores and subjective responses to alcohol. This study addresses this gap in the literature by testing the relationship between subjective responses to alcohol during alcohol administration and DAQ scores assessed 1 month later. Method: Individuals with alcohol dependence (n = 32) completed a randomized, single-blinded, intravenous alcohol administration in the laboratory in which subjective responses to the alcohol were measured, followed by a visit to the laboratory 1 month later to complete the DAQ. Results: Analyses revealed robust associations between DAQ scores and alcohol craving during alcohol administration (partial correlations: r = .43-.50, ps < .01), with the exception of the positive reinforcement subscale (r = .20, p = .30). Subjective intoxication and sedation were only associated with the negative reinforcement subscale of the DAQ (r = .38, p < .05 and r = .33, p < .05, respectively). Conclusions: Craving, captured by the DAQ, is reliably and positively associated with alcohol-induced craving. The DAQ is also associated with specific dimensions of subjective responses to alcohol. These results support the clinical utility of the DAQ, particularly in large samples where experimental manipulations may not be feasible.
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