King AC, de Wit H, McNamara PJ, Cao D. Rewarding, stimulant, and sedative alcohol responses and relationship to future binge drinking. Arch Gen Psychiatry. 68: 389-399

Department of Psychiatry and Behavioral Neuroscience, The University of Chicago, Chicago, IL 60637, USA.
Archives of general psychiatry (Impact Factor: 14.48). 04/2011; 68(4):389-99. DOI: 10.1001/archgenpsychiatry.2011.26
Source: PubMed


Excessive consumption of alcohol is a major problem in the United States and abroad. Despite many years of study, it is unclear why some individuals drink alcohol excessively while others do not. It has been postulated that either lower or greater acute responses to alcohol, or both, depending on the limb of the breath alcohol concentration curve, contribute to propensity for alcohol misuse.
To prospectively assess the relationship of acute alcohol responses to future binge drinking.
Within-subject, double-blind, placebo-controlled, multidose laboratory alcohol challenge study with intensive follow-up. Each participant completed 3 randomized sessions examining responses to a high (0.8 g/kg) and low (0.4 g/kg) alcohol dose and placebo, followed by quarterly assessments for 2 years examining drinking behaviors and alcohol diagnoses.
Participants recruited from the community.
High-risk heavy social drinkers aged 21 to 35 years who habitually engage in weekly binge drinking (n = 104) and light drinker controls (n = 86).
We conducted 570 laboratory sessions with a subsequent 99.1% follow-up (1506 of 1520).
Biphasic Alcohol Effects Scale, Drug Effects Questionnaire, cortisol response, Timeline Follow-Back, Drinker Inventory of Consequences-Recent, and DSM-IV alcohol abuse and dependence.
Alcohol produced greater stimulant and rewarding (liking and wanting) responses and lower sedative and cortisol responses in heavy vs light drinkers. Among the heavy drinkers, greater positive effects and lower sedative effects after alcohol consumption predicted increased binge drinking frequency during follow-up. In turn, greater frequency of binge drinking during follow-up was associated with greater likelihood of meeting diagnostic criteria for alcohol abuse and dependence.
The widely held low level response theory and differentiator model should be revised: in high-risk drinkers, stimulant and rewarding alcohol responses even at peak breath alcohol concentrations are important predictors of future alcohol problems. Identifier: NCT00961792.

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    • "The alcoholic beverage consisted of 16% volume ethanol, which contained 190-proof ethanol mixed with water, grape-flavored drink mix, and a sucralose-based sugar substitute. The alcohol dose was 0.8 g/kg, that is, equivalent to 4–5 standard alcohol drinks (King et al., 2011; Zhuang et al., 2012). The placebo beverage included 1% volume ethanol as a taste mask to reduce expectancy effects. "
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    ABSTRACT: Alcohol-related driving accidents and fatalities occur most frequently at nighttime and at dawn, that is, a mesopic lighting condition in which visual processing depends on both rod and cone photoreceptors. The temporal functions of the rod and cone pathways are critical for driving in this lighting condition. However, how alcohol influences the temporal functions in the rod and cone pathways at mesopic light levels is inconclusive. To address this, this study investigated whether an acute intoxicating dose of alcohol impairs rod- and/or cone-mediated critical fusion frequency (CFF; the lowest frequency of which an intermittent or flickering light stimulus is perceived as steady). In Experiment I, we measured the CFFs for 3 types of visual stimuli (rod stimulus alone, cone stimulus alone, and the mixture of both stimuli types), under 3 illuminant light levels (dim illuminance: 2 Td; low illuminance: 20 Td; and medium illuminance: 80 Td) in moderate-heavy social drinkers before and after they consumed an intoxicating dose of alcohol (0.8 g/kg) compared with a placebo beverage. In Experiment II, we examined whether the illuminance level (dark vs. light) of the visual area surrounding the test stimuli alters alcohol's effect on the temporal processing of rods and cones. The results showed that compared with placebo, alcohol significantly reduced CFFs of all stimulus types at all illuminance levels. Furthermore, alcohol intoxication produced a larger impairment on rod-pathway-mediated CFFs under light versus dark surround. These results indicate that alcohol intake slows down rod and cone-pathway-mediated temporal processing. Further research may elucidate whether this effect may play a role in alcohol-related injury and accidents, which often occur under low-light conditions. Copyright © 2015 by the Research Society on Alcoholism.
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    • "Specifically, acute sedation may positively predict craving for alcohol within a given drinking episode, yet chronically heightened sedation may be protective in the long term. It is also possible that sedation on the descending limb, not the ascending limb, is protective against future dependence; however, longitudinal studies have shown sedation at peak BrAC to be as predictive of future dependence as descending limb sedation (King et al. 2014, 2011). Lastly, while the present results are in line with the differentiator model with respect to stimulation , the positive associations between SR and craving across both stimulation and sedation are more difficult to square with the LR model (Schuckit 1994). "
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    ABSTRACT: Pre-clinical neurobiological models of addiction etiology including both the allostatic model and incentive sensitization theory suggest that alcohol consumption among alcohol-dependent (AD) individuals will be dissociated from hedonic reward as positive reinforcement mechanisms wane in later stage dependence. The aims of this study are to test this claim in humans by examining the relationship between dimensions of subjective responses to alcohol (SR) and alcohol craving across levels of alcohol exposure. Non-treatment-seeking drinkers (n = 205) completed an i.v. alcohol challenge (final target breath alcohol concentration = 0.06 g/dl) and reported on SR and craving. Participants were classified as light-to-moderate drinkers (LMD), heavy drinkers (HD) or AD. Analyses examined group differences in SR and craving response magnitude, as well as concurrent and predictive associations between SR domains and craving. At baseline, LMD and AD reported greater stimulation than HD, which carried over post-alcohol administration. However, stimulation was dose-dependently associated with alcohol craving in HD only. Furthermore, lagged models found that stimulation preceded craving among HD only, whereas this hypothesized pattern of results was not observed for craving preceding stimulation. Sedation was also positively associated with craving, yet no group differences were observed. In agreement with the prediction of diminished positive reinforcement in alcohol dependence, this study showed that stimulation/hedonic reward from alcohol did not precede craving in AD, whereas stimulation was dose-dependently associated with and preceded craving among non-dependent HD. © 2015 Society for the Study of Addiction.
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    • "An important characteristic of AUD is compromised impulse control and decision making, which has been implicated in the development and maintenance of the disorder , as well as the likelihood of relapse (Garavan and Stout 2005; De Wit 2009; Rogers et al. 2010; Dalley et al. 2011; Fineberg et al. 2014). Thus, personality traits such as impulsivity , i.e., the tendency to act without consideration of possible consequences, and suboptimal decision making are alleged risk factors for AUD (Dom et al. 2006; Johnson et al. 2008; de Wit 2009; Goudriaan et al. 2011; King et al. 2011; Dalley et al. 2011). Conversely, AUD patients show maladaptive decision making and reduced impulse control (Bechara et al. 2001; Salgado et al. 2009; Kim et al. 2011; MacKillop et al. 2011; Tomassini et al. 2012; Voon et al. 2014). "
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