Alcohol Underage Drinking Iowa Substance Abuse Brief, October 2022, Issue 10

The harmful use of alcohol results in three million worldwide worldwide deaths every year. In the United State, the Centers for disease control and prevention estimates that the harmful use of alcohol in more then 140,00 deaths each year. This document shows the mortality date from the Department of Health and Human Services

Alcohol use disorder causes global changes in splicing in the human brain

Alcohol use disorder (AUD) is a widespread disease leading to the deterioration of cognitive and other functions. Mechanisms by which alcohol affects the brain are not fully elucidated. Splicing constitutes a nuclear process of RNA maturation, which results in the formation of the transcriptome. We tested the hypothesis as to whether AUD impairs splicing in the superior frontal cortex (SFC), nucleus accumbens (NA), basolateral amygdala (BLA), and central nucleus of the amygdala (CNA). To evaluate splicing, bam files from STAR alignments were indexed with samtools for use by rMATS software. Computational analysis of affected pathways was performed using Gene Ontology Consortium, Gene Set Enrichment Analysis, and LncRNA Ontology databases. Surprisingly, AUD was associated with limited changes in the transcriptome: expression of 23 genes was altered in SFC, 14 in NA, 102 in BLA, and 57 in CNA. However, strikingly, mis-splicing in AUD was profound: 1421 mis-splicing events were detected in SFC, 394 in NA, 1317 in BLA, and 469 in CNA. To determine the mechanism of mis-splicing, we analyzed the elements of the spliceosome: small nuclear RNAs (snRNAs) and splicing factors. While snRNAs were not affected by alcohol, expression of splicing factor heat shock protein family A (Hsp70) member 6 (HSPA6) was drastically increased in SFC, BLA, and CNA. Also, AUD was accompanied by aberrant expression of long noncoding RNAs (lncRNAs) related to splicing. In summary, alcohol is associated with genome-wide changes in splicing in multiple human brain regions, likely due to dysregulation of splicing factor(s) and/or altered expression of splicing-related lncRNAs

“Wide-Awake Drunk”: Observing the Combined Effects of Alcohol and Caffeine on Somatic Withdrawal Signs in C57BL/6J Mice

Caffeine is one of the most widely used psychoactive stimulants in the world and is often used in combination with other substances. The combination of caffeine and alcohol has been shown to induce a stimulated, rather than sedated state, which may result in increased alcohol-attributable accidents (e.g., drunk driving, unprotected sex, and over intoxication). Preclinical research has found mixed results regarding the co-consumption of caffeine and alcohol – some found that caffeine increases alcohol intake while others the opposite. The current study expanded on previous research by testing the effects of combined caffeine and alcohol exposure in a binge-like, mouse paradigm. It was anticipated that the mice would consume larger amounts of alcohol in combination with caffeine compared to consuming either alcohol or caffeine alone. The present study explored drinking behaviors in 24 adult C57BL/6J mice using an intermittent access 2-bottle choice paradigm. Singly-housed mice were presented with one bottle of tap water and one bottle of tap water with incrementally increasing concentrations of alcohol (3-20% v/v), caffeine (0.01-0.05% w/v), or a mixture of alcohol and caffeine every other day. The amount of liquid consumed from each bottle was recorded at the same time every day and, approximately 24 hours after the last drinking day, mice were videotaped to assess somatic signs of alcohol or caffeine withdrawal. We hypothesized that mice in the combined alcohol and caffeine condition would drink more than the other conditions and that their physical dependence, as evidenced by increased somatic signs, would be greater than after consuming either drug alone

Mental Contrasting With Implementation Intentions Reduces Drinking When Drinking Is Hazardous: An Online Self-Regulation Intervention

Introduction. Drinking alcohol has detrimental health consequences, and effective interventions to reduce hazardous drinking are needed. The self-regulation intervention of Mental Contrasting with Implementation Intentions (MCII) promotes behavior change across a variety of health behaviors. In this study, we tested if online delivery of MCII reduced hazardous drinking in people who were worried about their drinking. Method. Participants (N = 200, female = 107) were recruited online. They were randomized to learn MCII or solve simple math problems (control). Results. Immediately after the intervention, participants in the MCII condition (vs. control) reported an increased commitment to reduce drinking. After 1 month, they reported having taken action measured by the Readiness to Change drinking scale. When drinking was hazardous (Alcohol Use Disorders Identification Test ≥ 8, n = 85), participants in the MCII condition indicated a decreased number of drinking days, exp(β) = 0.47, CI (confidence interval) [−1.322, −.207], p = .02, and drinks per week, exp(β) = 0.57, CI [0.94, 5.514], p = .007, compared with the control condition. Discussion. These findings demonstrate that a brief, self-guided online intervention (Mdn = 28 minutes) can reduce drinking in people who worry about their drinking. Our findings show a higher impact in people at risk for hazardous drinking. Conclusion. MCII is scalable as an online intervention. Future studies should test the cost-effectiveness of the intervention in real-world settings

LSD Administered as a Single Dose Reduces Alcohol Consumption in C57BL/6J Mice

There is a substantive clinical literature on classical hallucinogens, most commonly lysergic acid diethylamide (LSD) for the treatment of alcohol use disorder. However, there has been no published research on the effect of LSD on alcohol consumption in animals. This study evaluated the effect of LSD in mice using a two-bottle choice alcohol drinking paradigm. Adult male C57BL/6J mice were exposed to ethanol to develop preference and divided into three groups of equal ethanol consumption, and then treated with single intraperitoneal injection of saline or 25 or 50 μg/kg LSD and offered water and 20% ethanol. The respective LSD-treated groups were compared to the control group utilizing a multilevel model for repeated measures. In mice treated with 50 μg/kg LSD ethanol consumption was reduced relative to controls (p = 0.0035), as was ethanol preference (p = 0.0024), with a group mean reduction of ethanol consumption of 17.9% sustained over an interval of 46 days following LSD administration. No significant effects on ethanol consumption or preference were observed in mice treated with 25 μg/kg LSD. Neither total fluid intake nor locomotor activity in the LSD-treated groups differed significantly from controls. These results suggest that classical hallucinogens in the animal model merit further study as a potential approach to the identification of targets for drug discovery and investigation of the neurobiology of addiction

Differences in White Matter Microstructure and Connectivity in Nontreatment‐Seeking Individuals with Alcohol Use Disorder

Background Diffusion‐weighted imaging (DWI) has been widely used to investigate the integrity of white matter (WM; indexed by fractional anisotropy [FA]) in alcohol dependence and cigarette smoking. These disorders are highly comorbid, yet cigarette use has often not been adequately controlled in neuroimaging studies of alcohol‐dependent populations. In addition, information on WM deficits in currently drinking, nontreatment‐seeking (NTS) individuals with alcohol dependence is limited. Therefore, the aim of this work was to investigate WM microstructural integrity in alcohol use disorder by comparing matched samples of cigarette smoking NTS and social drinkers (SD). Methods Thirty‐eight smoking NTS and 19 smoking SD subjects underwent DWI as well as structural magnetic resonance imaging. After an in‐house preprocessing of the DWI data, FA images were analyzed with tract‐based spatial statistics (TBSS). FA obtained from the TBSS skeleton was tested for correlation with recent alcohol consumption. Results Smoking NTS had lower FA relative to smoking SD, predominantly in the left hemisphere (p < 0.05, family‐wise error rate corrected across FA skeleton). Across the full sample, FA and number of drinks per week were negatively related (ρ = −0.348, p = 0.008). Qualitative analyses of the structural connections through compromised WM as identified by TBSS showed differential connectivity of gray matter in NTS compared to SD subjects of left frontal, temporal, and parietal regions. Conclusions NTS subjects had lower WM FA than SD, indicating compromised WM integrity in the NTS population. The inverse relationship of entire WM skeleton FA with self‐reported alcohol consumption supports previous evidence of a continuum of detrimental effects of alcohol consumption on WM. These results provide additional evidence that alcohol dependence is associated with reduced WM integrity in currently drinking NTS alcohol‐dependent individuals, after controlling for the key variable of cigarette smoking

A preclinical model for identifying rats at risk of alcohol use disorder.

Alcohol use is one of the world's leading causes of death and disease, although only a small proportion of individuals develop persistent alcohol use disorder (AUD). The identification of vulnerable individuals prior to their chronic intoxication remains of highest importance. We propose here to adapt current methodologies for identifying rats at risk of losing control over alcohol intake by modeling diagnostic criteria for AUD: inability to abstain during a signaled period of reward unavailability, increased motivation assessed in a progressive effortful task and persistent alcohol intake despite aversive foot shocks. Factor analysis showed that these three addiction criteria loaded on one underlying construct indicating that they represent a latent construct of addiction trait. Further, not only vulnerable rats displayed higher ethanol consumption, and higher preference for ethanol over sweetened solutions, but they also exhibited pre-existing higher anxiety as compared to resilient rats. In conclusion, the present preclinical model confirms that development of an addiction trait not only requires prolonged exposure to alcohol, but also depends on endophenotype like anxiety that predispose a minority of individuals to lose control over alcohol consumption

Long-Chain ω-3 Levels Are Associated With Increased Alcohol Sensitivity in a Population-Based Sample of Adolescents.

BackgroundThe levels of the ω-3 long-chain polyunsaturated fatty acids (ω-3 LC-PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been associated with alcohol sensitivity in vertebrate and invertebrate model systems, but prior studies have not examined this association in human samples despite evidence of associations between ω-3 LC-PUFA levels and alcohol-related phenotypes. Both alcohol sensitivity and ω-3 LC-PUFA levels are impacted by genetic factors, and these influences may contribute to observed associations between phenotypes. Given the potential for using EPA and DHA supplementation in adjuvant care for alcohol misuse and other outcomes, it is important to clarify how ω-3 LC-PUFA levels relate to alcohol sensitivity.MethodsAnalyses were conducted using data from the Avon Longitudinal Study of Parents and Children. Plasma ω-3 LC-PUFA levels were measured at ages 15.5 and 17.5. Participants reported on their initial alcohol sensitivity using the early drinking Self-Rating of the Effects of Alcohol (SRE-5) scale, for which more drinks needed for effects indicates lower levels of response per drink, at ages 15.5, 16.5, and 17.5. Polygenic liability for alcohol consumption, alcohol problems, EPA levels, and DHA levels was derived using summary statistics from large, publicly available datasets. Linear regressions were used to examine the cross-sectional and longitudinal associations between ω-3 LC-PUFA levels and SRE scores.ResultsAge 15.5 ω-3 LC-PUFA levels were negatively associated with contemporaneous SRE scores and with age 17.5 SRE scores. One modest association (p = 0.02) between polygenic liability and SRE scores was observed, between alcohol problems-based polygenic risk scores (PRS) and age 16.5 SRE scores. Tests of moderation by genetic liability were not warranted.ConclusionsPlasma ω-3 LC-PUFA levels may be related to initial sensitivity to alcohol during adolescence. These data indicate that diet-related factors have the potential to impact humans' earliest responses to alcohol exposure