High-intensity sweet taste as a predictor of subjective alcohol responses to the ascending limb of an intravenous alcohol prime: an fMRI study.

High-intensity sweet-liking has been linked to alcohol use disorder (AUD) risk. However, the neural underpinning of this association is poorly understood. To find a biomarker predictive of AUD, 140 participants (social and heavy drinkers, ages 21-26) underwent functional magnetic resonance imaging (fMRI) during a monetary incentive delay (MID) task and stimulation with high (Sucrose)- and low-concentration sucrose, as well as viscosity-matched water.

Effects of moderate alcohol levels on default mode network connectivity in heavy drinkers.

Background: It is well established that even moderate levels of alcohol affect cognitive functions such as memory, self-related information processing, and response inhibition. Nevertheless, the neural mechanisms underlying these alcohol-induced changes are still unclear, especially on the network level. The default mode network (DMN) plays an important role in memory and self-initiated mental activities; hence, studying functional interactions of the DMN may provide new insights into the neural mechanisms underlying alcohol-related changes.

Translating preclinical models of alcohol seeking and consumption into the human laboratory using intravenous alcohol self-administration paradigms.

Preclinical models of alcohol use disorder (AUD) have advanced theoretical, mechanistic, and pharmacological study of the human condition. "Liking" and "wanting" behaviors reflect core processes underlying several models of AUD. However, the development and application of translational models of these preclinical approaches are at an incipient stage.

Subjective Responses to Alcohol in the Development and Maintenance of Alcohol Use Disorder.

Objective: Alcohol use disorder (AUD) remains an urgent public health problem. Longitudinal data are needed to clarify the role of acute subjective responses to alcohol in the development and maintenance of excessive drinking and AUD. The authors report on 10 years of repeated examination of acute alcohol responses in the Chicago Social Drinking Project.

Intoxication Effects on Impulsive Alcohol Choice in Heavy Drinkers: Correlation With Sensation Seeking and Differential Effects by Commodity.

Background: The preference for immediate rewards and high sensation seeking are both potent risk factors for alcohol use disorder (AUD), but how they interact during intoxication is poorly understood. To model decision making linked to AUD risk, we tested heavy drinkers for impulsive choice (delay discounting with alcohol:money or money:money) and behavioral sensation seeking using a novel odor choice task. Laboratory tasks measured actual behavior with real contingencies.

To Infuse or Ingest in Human Laboratory Alcohol Research.

Human alcohol laboratory studies use two routes of alcohol administration: ingestion and infusion. The goal of this paper was to compare and contrast these alcohol administration methods. The work summarized in this report was the basis of a 2019 Research Society on Alcoholism Roundtable, "To Ingest or Infuse: A Comparison of Oral and Intravenous Alcohol Administration Methods for Human Alcohol Laboratory Designs.

The role of alcohol response phenotypes in the risk for alcohol use disorder.

Heavy alcohol use is pervasive and one of our most significant global health burdens. Early theories posited that certain alcohol response phenotypes, notably low sensitivity to alcohol ('low-level response') imparts risk for alcohol use disorder (AUD). However, other theories, and newer measures of subjective alcohol responses, have challenged that contention and argued that high sensitivity to some alcohol effects are equally important for AUD risk.

Pairing neutral cues with alcohol intoxication: new findings in executive and attention networks.

Rationale: Alcohol-associated stimuli capture attention, yet drinkers differ in the precise stimuli that become paired with intoxication.

Objectives: Extending our prior work to examine the influence of alcoholism risk factors, we paired abstract visual stimuli with intravenous alcohol delivered covertly and examined brain responses to these Pavlovian-conditioned stimuli in fMRI when subjects were not intoxicated.

Methods: Sixty healthy drinkers performed task-irrelevant alcohol conditioning that presented geometric shapes as conditioned stimuli.

Alcohol affects the P3 component of an adaptive stop signal task ERP.

Background: The P3 component of the event-related potential (ERP) has been particularly useful in alcohol research for identifying endophenotypes of alcohol-use disorder (AUD) risk in sober subjects. However, practice and/or fatigue reduce P3 amplitude, limiting the ability to ascertain acute and adaptive effects of alcohol exposure. Here, we report acute alcohol effects on P3 amplitude and latency using an adaptive stop signal task (aSST).

A Prospective 5-Year Re-examination of Alcohol Response in Heavy Drinkers Progressing in Alcohol Use Disorder.

Background: The main neurobiological theories of the development of addiction, including tolerance, sensitization, incentive-sensitization, and allostasis, have not been tested in longitudinal human alcohol response research. To address this issue, we conducted the first controlled prospective investigation of subjective and neuroendocrine responses to alcohol measured over a 5-year interval in at-risk young adult heavy drinkers (HD) and light drinker control subjects.

Methods: Participants were 156 individuals, 86 heavy drinkers and 70 light drinkers, undergoing an initial oral alcohol challenge testing (.

The apéritif effect: Alcohol's effects on the brain's response to food aromas in women.

Objective: Consuming alcohol prior to a meal (an apéritif) increases food consumption. This greater food consumption may result from increased activity in brain regions that mediate reward and regulate feeding behavior. Using functional magnetic resonance imaging, we evaluated the blood oxygenation level dependent (BOLD) response to the food aromas of either roast beef or Italian meat sauce following pharmacokinetically controlled intravenous infusion of alcohol.

Adaptation of Subjective Responses to Alcohol is Affected by an Interaction of GABRA2 Genotype and Recent Drinking.

Background: Subjective perceptions of alcohol intoxication are associated with altered risk for alcohol abuse and dependence. Acute adaptation of these perceptions may influence such risk and may involve genes associated with pleasant perceptions or the relief of anxiety. This study assessed the effect of variation in the GABAA receptor genes GABRG1 and GABRA2 and recent drinking history on the acute adaptation of subjective responses to alcohol.

Beer self-administration provokes lateralized nucleus accumbens dopamine release in male heavy drinkers.

Rationale: Although striatal dopamine (DA) is important in alcohol abuse, the nature of DA release during actual alcohol drinking is unclear, since drinking includes self-administration of both conditioned flavor stimuli (CS) of the alcoholic beverage and subsequent intoxication, the unconditioned stimulus (US).

Objectives: Here, we used a novel self-administration analog to distinguish nucleus accumbens (NAcc) DA responses specific to the CS and US.

Methods: Right-handed male heavy drinkers (n = 26) received three positron emission tomography (PET) scans with the D2/D3 radioligand [(11)C]raclopride (RAC) and performed a pseudo self-administration task that separately administered a flavor CS of either a habitually consumed beer or the appetitive control Gatorade®, concomitant with the US of ethanol intoxication (0.

Family history of alcoholism interacts with alcohol to affect brain regions involved in behavioral inhibition.

Rationale: Impulsive behavior is associated with both alcohol use disorders and a family history of alcoholism (FHA). One operational definition of impulsive behavior is the stop-signal task (SST) which measures the time needed to stop a ballistic hand movement.

Objective: Employ functional magnetic resonance imaging (fMRI) to study right frontal responses to stop signals in heavy drinking subjects with and without FHA, and as a function of alcohol exposure.

System identification to characterize human use of ethanol based on generative point-process models of video games with ethanol rewards.

The influence of family history and genetics on the risk for the development of abuse or dependence is a major theme in alcoholism research. Recent research have used endophenotypes and behavioral paradigms to help detect further genetic contributions to this disease. Electronic tasks, essentially video games, which provide alcohol as a reward in controlled environments and with specified exposures have been developed to explore some of the behavioral and subjective characteristics of individuals with or at risk for alcohol substance use disorders.

Limbic responses to reward cues correlate with antisocial trait density in heavy drinkers.

Antisocial traits are common among alcoholics- particularly in certain subtypes. Although people with antisocial tendencies show atypical brain activation in some emotion and reward paradigms, how the brain reward systems of heavy drinkers (HD) are influenced by antisocial traits remains unclear. We used subjects' preferred alcohol drink odors (AO), appetitive (ApCO) and non-appetitive (NApO) control odors in functional magnetic resonance imaging (fMRI) to determine if reward system responses varied as a function of antisocial trait density (ASD).

Reliability of striatal [¹¹C]raclopride binding in smokers wearing transdermal nicotine patches.

Purpose: In studies where [(11)C]raclopride (RAC) positron emission tomography (PET) is used to assess changes in striatal dopamine, it is important to control for cognitive states, such as drug craving, that could alter dopamine levels. In cigarette smokers, transdermal nicotine patches (TNP) can control nicotine craving, but the effects of nicotine patches on RAC binding are unknown. Thus, we sought to determine the test-retest reliability of RAC binding in the presence of nicotine patches.

fMRI of the brain's response to stimuli experimentally paired with alcohol intoxication.

Rationale: Individuals learn associations between alcohol's sensory properties and intoxication, with such conditioned stimuli (CS) becoming involved in craving and relapse. However, these CS also carry idiosyncratic associations.

Objectives: This study aimed to test brain responses to novel CS conditioned with alcohol intoxication.

Subjective perceptions associated with the ascending and descending slopes of breath alcohol exposure vary with recent drinking history.

Background: The differentiator model predicts that individuals with a positive family history of alcoholism (FHA) or heavy alcohol consumers will feel more sensitive to the effects of alcohol on the ascending phase of the blood alcohol content while feeling less sedated on the descending phase. This study tested whether subjective perceptions are sensitive to the slope of breath alcohol concentration (BrAC) and whether that sensitivity is associated with an FHA and/or recent drinking history (RDH).

Methods: Family-history-positive (FHP, n = 27) and family-history-negative (FHN, n = 27) young adult nondependent drinkers were infused intravenously with alcohol in 2 sessions separated by 1 week.

A polymorphism in GABRA2 is associated with the medial frontal response to alcohol cues in an fMRI study.

Background: Significant evidence has accumulated to suggest an association between single-nucleotide polymorphisms (SNPs) in the GABRA2 gene and alcoholism. However, research has yet to show an association between these polymorphisms and the human brain's reward system function. In this study, we stratified subjects who had participated in an fMRI study of alcohol cue responses according to their genotype at a SNP in GABRA2 (rs279871) shown to be associated with alcohol dependence (Edenberg et al.

Single-nucleotide polymorphisms in corticotropin releasing hormone receptor 1 gene (CRHR1) are associated with quantitative trait of event-related potential and alcohol dependence.

Background: Endophenotypes reflect more proximal effects of genes than diagnostic categories, hence providing a more powerful strategy in searching for genes involved in complex psychiatric disorders. There is strong evidence suggesting the P3 amplitude of the event-related potential (ERP) as an endophenotype for the risk of alcoholism and other disinhibitory disorders. Recent studies demonstrated a crucial role of corticotropin releasing hormone receptor 1 (CRHR1) in the environmental stress response and ethanol self-administration in animal models.

Family history of alcoholism mediates the frontal response to alcoholic drink odors and alcohol in at-risk drinkers.

Although a family history of alcoholism is the strongest risk factor for developing alcohol dependence, there are few studies of the association between familial alcoholism and the human brain's reward system activity. We used functional magnetic resonance imaging (fMRI) to determine how family history affects the brain's response to subjects' preferred alcoholic drink odors (AO) as compared to appetitive control odors (ApCO). Fourteen non-dependent heavy drinkers (HD) who were family history positive (FHP) participated, as did 12 HD who were family history negative (FHN).

Priming deficiency in male subjects at risk for alcoholism: the N4 during a lexical decision task.

Background: While there is extensive literature on the relationship between the P3 component of event-related potentials (ERPs) and risk for alcoholism, there are few published studies regarding other potentially important ERP components. One important candidate is the N4(00) component in the context of semantic processing, as abnormalities in this component have been reported for adult alcoholics.

Method: A semantic priming task was administered to nonalcohol dependent male offspring (18 to 25 years) of alcoholic fathers [high risk (HR) n = 23] and nonalcoholic fathers [low risk (LR) n = 28] to study whether the 2 groups differ in terms of the N4 component.