Experimental psychopathology paradigms for alcohol use disorders: Applications for translational research

Bujarski, Spencer; Ray, Lara A.

doi:10.1016/j.brat.2016.05.008

Cited by 27 publications

(28 citation statements)

References 205 publications

(241 reference statements)

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“…Future studies could investigate the role of other hypothesized moderators and mediating mechanisms within this comprehensive model (Craske, 2016), or just focus on one of the manipulations in greater detail. Future translational research could employ EPIIC to evaluate the specific effects of intervention techniques within a controlled context (Bujarski & Ray, 2016). It is hoped such efforts will eventually inform new approaches to early intervention with impulsive youth.…”

Section: Discussionmentioning

confidence: 99%

“…Primary outcomes of interest were administered as repeated measures in order to reduce the potential impact of individual differences on induction effects. Laboratory alcohol consumption is influenced by body weight, sex, alcohol metabolism, drinking history, and many other factors that can be controlled for in a within-subjects design (Bujarski & Ray, 2016). The moderating effect of a heavy-drinking peer on alcohol consumption was also incorporated, such that half of all participants will engage in laboratory consumption with a confederate across both sessions (or not; between-subjects).…”

Section: Introductionmentioning

confidence: 99%

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A laboratory model of impulsivity and alcohol use in late adolescence

Gullo

Loxton

Price

et al. 2017

Behaviour Research and Therapy

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Impulsivity is a core characteristic of externalizing problems and a robust predictor of alcohol use in adolescence. There is little evidence on the causal mechanisms through which impulsivity influences drinking or how they are affected by key social factors (peer influence). This study reports the development of the first comprehensive laboratory model of adolescent impulsivity and alcohol use. One-hundred and twenty adolescents (50% female) of legal drinking age (M = 19.47 years, SD = 1.12) in Australia (18+ years) were subjected to 1 of 3 experimental manipulations to increase impulsive behavior (reward cue exposure, negative mood induction, ego depletion). Changes in disinhibition (stop-signal task) and reward-seeking (BAS-Fun Seeking) were measured before completing a laboratory drinking task alone or with a heavy-drinking confederate. Reward cue exposure increased alcohol consumption, with the effect mediated by increased reward-seeking. Negative mood induction increased disinhibition, but not drinking. The presence of a heavy-drinking peer directly increased alcohol consumption in an additive fashion. Findings provide causal evidence that extends survey-based research by highlighting the role of reward-related impulsivity in adolescent alcohol use. The new laboratory model can provide novel insights into the psychological processes underlying adolescent impulsivity and impulsivity-related drinking.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A laboratory model of impulsivity and alcohol use in late adolescence

Gullo

Loxton

Price

et al. 2017

Behaviour Research and Therapy

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“…The following well-validated (Bujarski and Ray, 2016;Mason and Higley, 2013) experimental paradigms were implemented to examine medication effects on subjective response to alcohol, cue reactivity, and stress reactivity:…”

Section: Experimental Procedures and Measuresmentioning

confidence: 99%

Development of the Neuroimmune Modulator Ibudilast for the Treatment of Alcoholism: A Randomized, Placebo-Controlled, Human Laboratory Trial

Ray

Bujarski

Shoptaw

et al. 2017

Neuropsychopharmacol

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109

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Current directions in medication development for alcohol use disorder (AUD) emphasize the need to identify novel molecular targets and efficiently screen new compounds aimed at those targets. Ibudilast (IBUD) is a neuroimmune modulator that inhibits phosphodiesterase-4 and -10 and macrophage migration inhibitory factor and was recently found to reduce alcohol intake in rats by ∼50%. To advance medication development for AUD, the present study consists of a randomized, crossover, double-blind, placebo-controlled laboratory study of IBUD in nontreatment-seeking individuals with current (ie, past month) mild-to-severe AUD. This study tested the safety, tolerability, and initial human laboratory efficacy of IBUD (50 mg b.i.d.) on primary measures of subjective response to alcohol as well as secondary measures of cue- and stress-induced changes in craving and mood. Participants (N=24) completed two separate 7-day intensive outpatient protocols that included daily visits for medication administration and testing. Upon reaching a stable target dose of IBUD (or matched placebo), participants completed a stress-exposure session (day 5; PM), an alcohol cue-exposure session (day 6; AM), and an i.v. alcohol administration session (day 6; PM). Participants stayed overnight after the alcohol administration, and discharge occurred on day 7 of the protocol. Medication conditions were separated by a washout period that was ⩾7 days. IBUD was well tolerated; however, there were no medication effects on primary measures of subjective response to alcohol. IBUD was associated with mood improvements on the secondary measures of stress exposure and alcohol cue exposure, as well as reductions in tonic levels of craving. Exploratory analyses revealed that among individuals with higher depressive symptomatology, IBUD attenuated the stimulant and mood-altering effects of alcohol as compared with placebo. Together, these findings extend preclinical demonstrations of the potential utility of IBUD for the treatment of AUD and suggest that depressive symptomatology should be considered as a potential moderator of efficacy for pharmacotherapies with neuroimmune effects, such as IBUD.

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“…The third category consists of alcohol self-administration paradigms in which individuals are given the opportunity to consume alcohol in the laboratory. As discussed in detail elsewhere, each paradigm has its own strengths and weaknesses (Bujarski and Ray, 2016), and can be leveraged to address a multitude of research questions (Ray et al, 2016). While the aforementioned experimental methods are widely used in the field of alcohol research, surprisingly few studies have examined the associations between subjective response to alcohol, craving for alcohol, and alcohol self-administration within individuals.…”

Section: Introductionmentioning

confidence: 99%

“…Subjective response to alcohol represents a multifaceted (Ray et al, 2009, Bujarski et al, 2015b and replicable construct (Roche et al, 2014, King et al, 2015. Moreover, alcohol administration methods include both intravenous and oral alcohol administration, with the first benefiting from tight controls over breath alcohol concentration (BrAC) and the later benefiting from greater ecological validity (Bujarski and Ray, 2016). While there are few direct comparisons of the two methods, an early study found them comparable in eliciting subjective response with the exception of craving which was significantly higher in the oral alcohol administration model (Ray et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

The Interplay Between Subjective Response to Alcohol, Craving, and Alcohol Self‐Administration in the Human Laboratory

Green

Grodin

Lim

et al. 2019

Alcoholism Clin & Exp Res

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Background: Despite a rich literature on human laboratory paradigms of subjective response to alcohol (SR), craving for alcohol, and alcohol self-administration, few studies have examined the interplay across these three constructs. The present study addresses this gap in the literature by examining the interplay between SR, craving, and self-administration in the human laboratory. Methods: Data were culled from a medication study (NCT02026011) in which heavy drinking participants of East Asian ancestry completed two double-blinded and counterbalanced experimental sessions. In each experimental session, participants received a priming dose of IV alcohol to a target breath alcohol concentration (BrAC) of 0.06 g/dl and measures of SR (stimulation and sedation) and alcohol craving were collected across rising BrACs. The IV alcohol challenge was immediately followed by a 1-hour alcohol self-administration period. Results: Mixed model analyses found a positive and significant relationship between the slope of stimulation and the slope of craving during the alcohol challenge. The relationship between sedation and craving, however, was not significant. The slope of craving during the alcohol challenge significantly predicted a higher number of mini-drinks consumed and lower latency to first drink. Further, mediation analyses found that craving was a significant mediator of the relationship between stimulation and total number of mini-drinks consumed, but the same pattern was not found for sedation. Conclusions: Insofar as alcohol self-administration represents the endpoint of interest for a host of experimental and clinical research questions, the present study suggests that alcohol craving represents a more proximal predictor of self-administration than measures of alcohol-induced stimulation. It is recommended that human laboratory models interpret measures of SR and craving in light of their relative predictive utility for drinking outcomes.

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Experimental psychopathology paradigms for alcohol use disorders: Applications for translational research

Cited by 27 publications

References 205 publications

A laboratory model of impulsivity and alcohol use in late adolescence

A laboratory model of impulsivity and alcohol use in late adolescence

Development of the Neuroimmune Modulator Ibudilast for the Treatment of Alcoholism: A Randomized, Placebo-Controlled, Human Laboratory Trial

The Interplay Between Subjective Response to Alcohol, Craving, and Alcohol Self‐Administration in the Human Laboratory

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