BACKGROUND: Human laboratory paradigms are a pillar in medication development for alcohol use disorders (AUD). Neuroimaging paradigms, in which individuals are exposed to cues that elicit neural correlates of alcohol craving (e.g., mesocorticolimbic activation), are increasingly utilized to test the effects of AUD medications. Elucidation of the translational effects of these neuroimaging paradigms on human laboratory paradigms, such as self-administration, is warranted. The current study is a secondary analysis examining whether alcohol cue-induced activation in the ventral striatum is predictive of subsequent alcohol self-administration in the laboratory. METHODS: Non-treatment-seeking heavy drinkers of East Asian descent (n = 41) completed a randomized, placebo-controlled, double-blind, crossover experiment on the effects of naltrexone on neuroimaging and human laboratory paradigms. Participants completed 5 days of study medication (or placebo); on day 4, they completed a neuroimaging alcohol taste cue-reactivity task. On the following day (day 5), participants completed a 60-minute alcohol self-administration paradigm. RESULTS: Multilevel Cox regressions indicated a significant effect of taste cue-elicited ventral striatum activation on latency to first drink, Wald χ2 = 2.88, p = 0.05, such that those with higher ventral striatum activation exhibited shorter latencies to consume their first drink. Similarly, ventral striatum activation was positively associated with total number of drinks consumed, F(1, 38) = 5.90, p = 0.02. These effects were significant after controlling for alcohol use severity, OPRM1 genotype, and medication. Other potential regions of interest (anterior cingulate, thalamus) were not predictive of self-administration outcomes. CONCLUSIONS: Neuroimaging alcohol taste cue paradigms may be predictive of laboratory paradigms such as self-administration. Elucidation of the relationships among different paradigms will inform how these paradigms may be used synergistically in experimental medicine and medication development.
BACKGROUND: Human laboratory paradigms are a pillar in medication development for alcohol use disorders (AUD). Neuroimaging paradigms, in which individuals are exposed to cues that elicit neural correlates of alcohol craving (e.g., mesocorticolimbic activation), are increasingly utilized to test the effects of AUD medications. Elucidation of the translational effects of these neuroimaging paradigms on human laboratory paradigms, such as self-administration, is warranted. The current study is a secondary analysis examining whether alcohol cue-induced activation in the ventral striatum is predictive of subsequent alcohol self-administration in the laboratory. METHODS: Non-treatment-seeking heavy drinkers of East Asian descent (n = 41) completed a randomized, placebo-controlled, double-blind, crossover experiment on the effects of naltrexone on neuroimaging and human laboratory paradigms. Participants completed 5 days of study medication (or placebo); on day 4, they completed a neuroimaging alcohol taste cue-reactivity task. On the following day (day 5), participants completed a 60-minute alcohol self-administration paradigm. RESULTS: Multilevel Cox regressions indicated a significant effect of taste cue-elicited ventral striatum activation on latency to first drink, Wald χ2 = 2.88, p = 0.05, such that those with higher ventral striatum activation exhibited shorter latencies to consume their first drink. Similarly, ventral striatum activation was positively associated with total number of drinks consumed, F(1, 38) = 5.90, p = 0.02. These effects were significant after controlling for alcohol use severity, OPRM1 genotype, and medication. Other potential regions of interest (anterior cingulate, thalamus) were not predictive of self-administration outcomes. CONCLUSIONS: Neuroimaging alcohol taste cue paradigms may be predictive of laboratory paradigms such as self-administration. Elucidation of the relationships among different paradigms will inform how these paradigms may be used synergistically in experimental medicine and medication development.
Authors: Patrick Bach; Georg Weil; Enrico Pompili; Sabine Hoffmann; Derik Hermann; Sabine Vollstädt-Klein; Karl Mann; Ursula Perez-Ramirez; David Moratal; Santiago Canals; Serdar M Dursun; Andrew J Greenshaw; Peter Kirsch; Falk Kiefer; Wolfgang H Sommer Journal: Addict Biol Date: 2019-02-12 Impact factor: 4.280
Authors: Marc A Schuckit; Tom L Smith; Martin P Paulus; Susan F Tapert; Alan N Simmons; Neil J Tolentino; Alexandra Shafir Journal: Alcohol Clin Exp Res Date: 2016-01 Impact factor: 3.455
Authors: Karl Mann; Sabine Vollstädt-Klein; Iris Reinhard; Tagrid Leménager; Mira Fauth-Bühler; Derik Hermann; Sabine Hoffmann; Ulrich S Zimmermann; Falk Kiefer; Andreas Heinz; Michael N Smolka Journal: Alcohol Clin Exp Res Date: 2014-11 Impact factor: 3.455
Authors: Francesca M Filbey; Lara Ray; Andrew Smolen; Eric D Claus; Amy Audette; Kent E Hutchison Journal: Alcohol Clin Exp Res Date: 2008-07 Impact factor: 3.455
Authors: Anne Beck; Torsten Wüstenberg; Alexander Genauck; Jana Wrase; Florian Schlagenhauf; Michael N Smolka; Karl Mann; Andreas Heinz Journal: Arch Gen Psychiatry Date: 2012-08
Authors: Marsha E Bates; Laura M Lesnewich; Sarah Grace Uhouse; Suril Gohel; Jennifer F Buckman Journal: Front Psychiatry Date: 2019-09-05 Impact factor: 4.157