scholarly journals Translational opportunities in animal and human models to study alcohol use disorder

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Steven J. Nieto ◽  
Erica N. Grodin ◽  
Claudia G. Aguirre ◽  
Alicia Izquierdo ◽  
Lara A. Ray
Keyword(s):  
Alcohol Use ◽  
Alcohol Use Disorder ◽  
Animal Species ◽  
Experimental Models ◽  
Future Directions ◽  
Reverse Translation ◽  
Approaches To Study ◽  
Preclinical And Clinical Studies ◽  
Laboratory Models ◽  
Human Laboratory

AbstractAnimal and human laboratory paradigms offer invaluable approaches to study the complex etiologies and mechanisms of alcohol use disorder (AUD). We contend that human laboratory models provide a “bridge” between preclinical and clinical studies of AUD by allowing for well-controlled experimental manipulations in humans with AUD. As such, examining the consilience between experimental models in animals and humans in the laboratory provides unique opportunities to refine the translational utility of such models. The overall goal of the present review is to provide a systematic description and contrast of commonly used animal paradigms for the study of AUD, as well as their human laboratory analogs if applicable. While there is a wide breadth of animal species in AUD research, the paradigms discussed in this review rely predominately on rodent research. The overarching goal of this effort is to provide critical analysis of these animal models and to link them to human laboratory models of AUD. By systematically contrasting preclinical and controlled human laboratory models, we seek to identify opportunities to enhance their translational value through forward and reverse translation. We provide future directions to reconcile differences between animal and human work and to improve translational research for AUD.

Alcohol Use Disorder

2018 ◽  
Author(s):  
Igor Ponomarev
Keyword(s):  
Alcohol Use ◽  
Alcohol Use Disorder ◽  
Critical Discussion ◽  
Epigenetic Mechanisms ◽  
Future Directions ◽  
Clinically Significant ◽  
Early Life Exposures ◽  
The Brain ◽  
Epigenetic Research

Alcohol use disorder (AUD) is characterized by clinically significant impairments in health and social function. Epigenetic mechanisms of gene regulation may provide an attractive explanation for how early life exposures to alcohol contribute to the development of AUD and exert lifelong effects on the brain. This chapter provides a critical discussion of the role of epigenetic mechanisms in AUD etiology and the potential of epigenetic research to improve diagnosis, evaluate risks for alcohol-induced pathologies, and promote development of novel therapies for the prevention and treatment of AUD. Challenges of the current epigenetic approaches and future directions are also discussed.

scholarly journals Alcohol Tolerance in Human Laboratory Studies for Development of Medications to treat Alcohol Use Disorder

2020 ◽  
Vol 55 (2) ◽  
pp. 129-135
Author(s):  
Carolina L Haass-Koffler ◽  
Roberta Perciballi
Keyword(s):  
Alcohol Use ◽  
Alcohol Use Disorder ◽  
Motor Impairment ◽  
Alcohol Tolerance ◽  
Subjective Response ◽  
Laboratory Studies ◽  
Phenotypic Profile ◽  
Additional Information ◽  
Research Opportunity ◽  
Human Laboratory

Abstract Aims Human laboratory studies have contributed extensively in the research and development of novel medications to treat alcohol use disorder (AUD). Alcohol tolerance may represent one additional variable that can be utilized to expand the understanding of the AUD wide phenotypic profile and provide support to the medication development process. Tolerance is characterized as an individual’s subjective response to alcohol and has been recognized as a predictor of AUD progression. Tolerance can be evaluated both by self-reported response (e.g. assessments) and objective measurements (e.g. motor impairment); as such, it represents an exploitable variable in the field of alcohol research. Methods This Narrative Review focuses on the use of alcohol tolerance, specifically within alcohol laboratory studies, for medication development. It seeks to identify a research gap and a research opportunity in clinical studies to evaluate biobehavioral responses captured in order to develop medications to treat AUD. Results Alcohol tolerance may provide additional information on the safety and tolerability of medications to treat AUD, in particular, when novel medications are co-administered with alcohol within the AUD population. Conclusions As such, alcohol tolerance represents an additional outcome that may be included in randomized clinical trial (RCT) protocols designed for developing AUD pharmacotherapies.

Genetics in Experimental Psychopathology: From Laboratory Models to Therapygenetics. Where do we go from Here?

2015 ◽  
Vol a4 (2) ◽  
pp. 169-188 ◽  
Author(s):  
Tina B. Lonsdorf ◽  
Johanna M. P. Baas
Keyword(s):  
Individual Differences ◽  
Experimental Models ◽  
Stressful Events ◽  
Future Directions ◽  
Substantial Impact ◽  
Experimental Psychopathology ◽  
Current State ◽  
Underlying Processes ◽  
Exemplary Model ◽  
Laboratory Models

Experimental psychopathology is the application of experimental methods to the study of psychopathology and its underlying processes. The study of individual differences in the development, maintenance and/or relapse of psychopathology is currently at the forefront of research. Stressful events are known to exert a substantial impact on our lives. Why however, do some people react in an extremely adaptive way, while others develop pathology in the aftermath of a trauma? One particularly interesting individual differences factor is genetic makeup and the aim of this paper is to review the current state of the art of genetics in experimental psychopathology which is illustrated by using fear conditioning as an exemplary model in the study of mechanisms underlying anxiety. We identify and discuss current challenges of the field and provide recommendations on how these can be met. In addition, criteria for experimental models of psychopathology as well as future directions are discussed.

scholarly journals A novel human laboratory model for screening medications for alcohol use disorder

Trials ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Diana Ho ◽  
Brandon Towns ◽  
Erica N. Grodin ◽  
Lara A. Ray
Keyword(s):  
Clinical Trials ◽  
Alcohol Use ◽  
Early Phase ◽  
Alcohol Use Disorder ◽  
Internal Validity ◽  
Laboratory Model ◽  
Phase 2 ◽  
Motivation To Change ◽  
Quit Attempt ◽  
Human Laboratory

Abstract Background Alcohol use disorder (AUD) is a highly prevalent, chronic relapsing disorder with a high disease burden in the USA. Pharmacotherapy is a promising treatment method for AUD; however, the few FDA-approved medications are only modestly effective. Medications development for AUD is a high priority research area, but the cumbersome drug development process hinders many potential compounds from reaching approval. One area with major opportunities for improvement is the process of screening novel compounds for initial efficacy, also known as early phase 2 trials. Early phase 2 trials incorporate human laboratory paradigms to assess relevant clinical constructs, such as craving and subjective responses to alcohol. However, these controlled paradigms often lack the ecological validity of clinical trials. Therefore, early phase 2 trials can be more efficient and clinically meaningful if they combine the internal validity of experimental laboratory testing with the external validity of clinical trials. To that end, the current study aims to develop and validate a novel early efficacy paradigm, informed by smoking cessation literature, to screen novel medications for AUD. As an established AUD medication, naltrexone will serve as an active control to test both the practice quit attempt model and the efficacy of a promising AUD pharmacotherapy, varenicline. Methods Individuals with current AUD reporting intrinsic motivation to change their drinking will complete a week-long “practice quit attempt” while on study medication. Participants are randomized and blinded to either naltrexone, varenicline, or placebo. During the practice quit attempt, participants will complete daily visits over the phone and fill out online questionnaires regarding their drinking, alcohol craving, and mood. Additionally, participants will undergo two alcohol cue-reactivity sessions. Discussion The successful completion of this study will advance medications development by proposing and validating a novel early efficacy model for screening AUD pharmacotherapies, which in turn can serve as an efficient strategy for making go/no-go decisions as to whether to proceed with clinical trials. Trial registration ClinicalTrials.gov NCT04249882. Registered on 31 January 2020.

scholarly journals Neuroendocrine Response to Exogenous Ghrelin Administration, Combined With Alcohol, in Heavy-Drinking Individuals: Findings From a Randomized, Double-Blind, Placebo-Controlled Human Laboratory Study

2021 ◽  
Author(s):  
Mehdi Farokhnia ◽  
Kelly M Abshire ◽  
Aaron Hammer ◽  
Sara L Deschaine ◽  
Anitha Saravanakumar ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Alcohol Use Disorder ◽  
Heavy Drinking ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Alcohol Administration ◽  
Neuroendocrine Response ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Human Laboratory

Abstract Background Accumulating evidence has established a role for the orexigenic hormone ghrelin in alcohol-seeking behaviors. Accordingly, the ghrelin system may represent a potential pharmacotherapeutic target for alcohol use disorder. Ghrelin modulates several neuroendocrine pathways, such as appetitive, metabolic, and stress-related hormones, which are particularly relevant in the context of alcohol use. The goal of the present study was to provide a comprehensive assessment of neuroendocrine response to exogenous ghrelin administration, combined with alcohol, in heavy-drinking individuals. Methods This was a randomized, crossover, double-blind, placebo-controlled human laboratory study, which included 2 experimental alcohol administration paradigms: i.v. alcohol self-administration and i.v. alcohol clamp. Each paradigm consisted of 2 counterbalanced sessions of i.v. ghrelin or placebo administration. Repeated blood samples were collected during each session, and peripheral concentrations of the following hormones were measured: leptin, glucagon-like peptide-1, pancreatic polypeptide, gastric inhibitory peptide, insulin, insulin-like growth factor-1, cortisol, prolactin, and aldosterone. Results Despite some statistical differences, findings were consistent across the 2 alcohol administration paradigms: i.v. ghrelin, compared to placebo, increased blood concentrations of glucagon-like peptide-1, pancreatic polypeptide, cortisol, and prolactin, both acutely and during the whole session. Lower levels of leptin and higher levels of aldosterone were also found during the ghrelin vs placebo session. Conclusion These findings, gathered from a clinically relevant sample of heavy-drinking individuals with alcohol use disorder, provide a deeper insight into the complex interplay between ghrelin and appetitive, metabolic, and stress-related neuroendocrine pathways in the context of alcohol use.

DSM-5 alcohol use disorder features among treatment-seeking older adults

2018 ◽  
Vol 64 (4) ◽  
pp. 185-196 ◽  
Author(s):  
Silke Behrendt ◽  
Barbara Braun ◽  
Randi Bilberg ◽  
Gerhard Bühringer ◽  
Michael Bogenschutz ◽  
...  
Keyword(s):  
Older Adults ◽  
Alcohol Use ◽  
Alcohol Use Disorder ◽  
The Elderly ◽  
Treatment Seeking ◽  
Controlled Clinical Trial ◽  
Dsm 5 ◽  
Wide Range ◽  
And Gender ◽  
International Multicenter

Abstract. Background: The number of older adults with alcohol use disorder (AUD) is expected to rise. Adapted treatments for this group are lacking and information on AUD features in treatment seeking older adults is scarce. The international multicenter randomized-controlled clinical trial “ELDERLY-Study” with few exclusion criteria was conducted to investigate two outpatient AUD-treatments for adults aged 60+ with DSM-5 AUD. Aims: To add to 1) basic methodological information on the ELDERLY-Study by providing information on AUD features in ELDERLY-participants taking into account country and gender, and 2) knowledge on AUD features in older adults seeking outpatient treatment. Methods: baseline data from the German and Danish ELDERLY-sites (n=544) were used. AUD diagnoses were obtained with the Mini International Neuropsychiatric Interview, alcohol use information with Form 90. Results: Lost control, desired control, mental/physical problem, and craving were the most prevalent (> 70 %) AUD-symptoms. 54.9 % reported severe DSM-5 AUD (moderate: 28.2 %, mild: 16.9 %). Mean daily alcohol use was 6.3 drinks at 12 grams ethanol each. 93.9 % reported binging. More intense alcohol use was associated with greater AUD-severity and male gender. Country effects showed for alcohol use and AUD-severity. Conclusion: European ELDERLY-participants presented typical dependence symptoms, a wide range of severity, and intense alcohol use. This may underline the clinical significance of AUD in treatment-seeking seniors.

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