Peripheral blood transcriptomic profiling of molecular mechanisms commonly regulated by binge drinking and placebo effects.

Molecular responses to alcohol consumption are dynamic, context-dependent, and arise from a complex interplay of biological and external factors. While many have studied genetic risk associated with drinking patterns, comprehensive studies identifying dynamic responses to pharmacologic and psychological/placebo effects underlying binge drinking are lacking. We investigated transcriptome-wide response to binge, medium, and placebo alcohol consumption by 17 healthy heavy social drinkers enrolled in a controlled, in-house, longitudinal study of up to 12 days. Using RNA-seq, we identified 251 and 13 differentially expressed genes (DEGs) in response to binge drinking and placebo, respectively. Eleven protein-coding DEGs had very large effect sizes in response to binge drinking (Cohen's d > 1). Furthermore, binge dose significantly impacted the Cytokine-cytokine receptor interaction pathway (KEGG: hsa04060) across all experimental sequences. Placebo also impacted hsa04060, but only when administered following regular alcohol drinking sessions. Similarly, medium-dose and placebo commonly impacted KEGG pathways of Systemic lupus erythematosus, Neutrophil extracellular trap formation, and Alcoholism based on the sequence of drinking sessions. These findings together indicate the "dose-extending effects" of placebo at a molecular level. Furthermore, besides supporting alcohol dose-specific molecular changes, results suggest that the placebo effects may induce molecular responses within the same pathways regulated by alcohol.

The Influence of Stress and Binge-Patterned Alcohol Drinking on Mouse Skeletal Muscle Protein Synthesis and Degradation Pathways.

Adverse experiences (e.g., acute stress) and alcohol misuse can both impair skeletal muscle homeostasis, resulting in reduced protein synthesis and greater protein breakdown. Exposure to acute stress is a significant risk factor for engaging in alcohol misuse. However, little is known about how these factors together might further affect skeletal muscle health. To that end, this study investigated the effects of acute stress exposure followed by a period of binge-patterned alcohol drinking on signaling factors along mouse skeletal muscle protein synthesis (MPS) and degradation (MPD) pathways. Young adult male C57BL/6J mice participated in the Drinking in the Dark paradigm, where they received 2-4 h of access to 20% ethanol (alcohol group) or water (control group) for four days to establish baseline drinking levels. Three days later, half of the mice in each group were either exposed to a single episode of uncontrollable tail shocks (acute stress) or remained undisturbed in their home cages (no stress). Three days after stress exposure, mice received 4 h of access to 20% ethanol (alcohol) to model binge-patterned alcohol drinking or water for ten consecutive days. Immediately following the final episode of alcohol access, mouse gastrocnemius muscle was extracted to measure changes in relative protein levels along the Akt-mTOR MPS, as well as the ubiquitin-proteasome pathway (UPP) and autophagy MPD pathways via Western blotting. A single exposure to acute stress impaired Akt singling and reduced rates of MPS, independent of alcohol access. This observation was concurrent with a potent increase in heat shock protein seventy expression in the muscle of stressed mice. Alcohol drinking did not exacerbate stress-induced alterations in the MPS and MPD signaling pathways. Instead, changes in the MPS and MPD signaling factors due to alcohol access were primarily observed in non-stressed mice. Taken together, these data suggest that exposure to a stressor of sufficient intensity may cause prolonged disruptions to signaling factors that impact skeletal muscle health and function beyond what could be further induced by periods of alcohol misuse.

Binge Drinking Among Sports Gamblers.

This survey study examines whether or not individuals who wager on sports are at greater risk of binge use of alcohol.

Binge alcohol induces NRF2-related antioxidant response in the skeletal muscle of female mice.

BACKGROUND: Chronic alcohol enhances oxidative stress, but the temporal response of antioxidant genes in skeletal muscle following a binge drinking episode remains unknown. METHODS: Experiment 1: C57BL/6Hsd female mice received an IP injection of saline (CON; n = 39) or ethanol (ETOH; n = 39) (5 g/kg). Gastrocnemius muscles were collected from baseline (untreated; n = 3), CON (n = 3), and ETOH (n = 3) mice every 4 h for 48 h. Experiment 2: Gastrocnemius muscles were collected from control-fed (CON-FED; n = 17), control-fasted (CON-FAST; n = 18), or alcohol-fed (ETOH-FED; n = 18) mice every 4hrs for 20hrs after saline or ethanol (5 g/kg). RESULTS: EtOH enhanced Superoxide dismutase 1 (Sod1) and NADPH Oxidase 4 (Nox4) from 24 to 48hr after the binge, while Sod2 and Nox2 were suppressed. Nuclear factor erythroid-derived 2-like 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) increased 12hrs after intoxication. Cytochrome P450 oxidoreductase (Por), Heme oxygenase 1 (Ho1), Peroxiredoxin 6 (Prdx6), Glutamate-cysteine ligase catalytic subunit (Gclc), Glutamate-cysteine ligase modifier subunit (Gclm), and Glutathione-disulfide reductase (Gsr) were increased by ETOH starting 12-16hrs post-binge. Fasting had similar effects on Nrf2 compared to alcohol, but downstream targets of NRF2, including Por, Ho1, Gclc, and Gclm, were differentially altered with fasting and EtOH. CONCLUSION: These data suggest that acute alcohol intoxication induced markers of oxidative stress and antioxidant signaling through the NRF2 pathway and that there were effects of alcohol independent of a possible decrease in food intake caused by binge intoxication.

Brief emotion regulation strategies to reduce alcohol craving: Mediating role of state difficulties in emotion regulation.

OBJECTIVE: This study experimentally compared the effects of emotion regulation (ER) strategies on alcohol craving and examined the mediating effect of state difficulties in emotion regulation (S-DER) on the relationship between negative/positive emotion and alcohol craving. METHOD: 417 participants (76.74% women, Mage = 20.76 years) endorsing past-month heavy/binge drinking were randomly assigned to one of four ER conditions (positive reappraisal, distancing, distraction, and acceptance). Participants completed state assessments, including negative/positive emotion, S-DER, and alcohol craving, prior to (T0) and after (T1) engaging in a negative emotion induction task. Subsequently, participants completed an ER strategy task based on their assigned ER strategy condition and completed a third state assessment (T2). RESULTS: Time had a significant quadratic effect on alcohol craving, such that craving increased from T0 to T1 and decreased from T1 to T2. There was no significant effect of ER strategy condition on craving. Change in S-DER mediated the relationship between the change in negative/positive emotion and the change in craving, with emotional modulation and emotional acceptance facets of S-DER dominating the mediating effect during negative emotion induction and ER strategy induction, respectively. CONCLUSIONS: Results suggest interventions targeting S-DER's emotional modulation and acceptance facets could reduce acute craving when experiencing undesired emotions.

Exploring differences in substance use behaviours among gender minority and non-gender minority youth: a cross-sectional analysis of the COMPASS study. / Exploration des différences dans les comportements liés à la consommation de substances chez les jeunes faisant partie de minorités de genre et les jeunes ne faisant pas partie de minorités de genre : analyse transversale de l'étude COMPASS.

INTRODUCTION: Research characterizing substance use disparities between gender minority youth (GMY) and non-GMY (i.e. girls and boys) is limited. The aim of this study was to examine the differences in substance use behaviours among gender identity (GI) groups and identify associated risk and protective factors. METHODS: Cross-sectional data from Canadian secondary school students (n = 42 107) that participated in Year 8 (2019/20) or Year 9 (2020/21) of the COMPASS study were used. Hierarchal logistic regression models estimated current substance use (cigarettes, e-cigarettes, binge drinking, cannabis and nonmedical prescription opioids [NMPOs]). Predictor variables included sociodemographics, other substances, mental health outcomes, school connectedness, bullying and happy home life. Interaction terms were used to test mental health measures as moderators in the association between GI and substance use. RESULTS: Compared to non-GMY, GMY reported a higher prevalence for all substance use outcomes. In the adjusted analyses, GMY had higher odds of cigarette, cannabis and NMPO use and lower odds for e-cigarette use relative to non-GMY. The likelihood of using any given substance was higher among individuals who were involved with other substances. School connectedness and happy home life had a protective effect for all substances except binge drinking. Bullying victimization was associated with greater odds of cigarette, e-cigarette use and NMPOs. Significant interactions between GI and all mental health measures were detected. CONCLUSION: Findings highlight the importance of collecting a GI measure in youth population surveys and prioritizing GMY in substance use-related prevention, treatment and harm reduction programs. Future studies should investigate the effects of GI status on substance use onset and progression among Canadian adolescents over time.

Physical training mitigates alveolar bone and blood enzymatic antioxidants defense impairment induced by binge ethanol consumption in rats.

We aimed to investigate the effectiveness of physical training as a protective strategy to mitigate alveolar bone damage and blood antioxidant defense caused by ethanol (EtOH) consumption in a binge-drinking pattern. Male Wistar rats aged approximately 90 days were divided into four groups: control, training, EtOH, and training + EtOH. The physical training protocol was conducted on a treadmill for four consecutive weeks, while the animals in the EtOH group were administered EtOH via orogastric gavage for three consecutive days each week, following the binge drink pattern. After the training period, blood and mandibles were collected for plasma oxidative biochemistry analysis, and the alveolar bone was subjected to physicochemical composition analysis, tissue evaluation, and microtomography evaluation. Our results showed that EtOH induced oxidative stress and physical exercise promoted the recovery of antioxidant action. Physical training minimized the damage to the mineral/matrix composition of the alveolar bone due to EtOH consumption and increased the density of osteocytes in the trained group treated with EtOH than in those exposed only to EtOH. Furthermore, physical training reduced damage to the alveolar bone caused by EtOH consumption. Our findings suggest that physical training can serve as an effective strategy to reduce systemic enzymatic oxidative response damage and alleviate alveolar bone damage resulting from alcohol consumption. Further investigations are warranted to elucidate the underlying mechanisms and explore, in addition to physical training, the potential effects of other activities with varying intensities on managing alcohol-induced bone damage.

Binge drinking associated with mean temperature: a cross-sectional study among Mexican adults living in cities.

BACKGROUND: The association between environmental temperature and alcohol consumption has not been widely explored despite the potential that increasing temperatures could promote the consumption of alcoholic beverages and the alcohol-related burden of disease. We aimed to explore the association between temperature and binge drinking in Mexican adults from urban cities, overall, and by alcoholic beverage type. METHODS: Data on 10,552 adults ≥ 18 years was obtained from the 2016 National Survey on Drug, Alcohol, and Tobacco Consumption. The mean annual temperature at the municipality was obtained from the Mexican National Weather Service using monthly temperatures from 2015 to 2016. We analyzed binge drinking for all alcoholic beverages in the last year and by type of alcohol as beer, liquor, wine, and coolers. Associations between mean temperature over the past year and binge drinking over the past year among current drinkers were estimated using multilevel Poisson models with robust standard errors adjusted for age, sex, education level, marital status, and household socioeconomic status, with a fixed effect by region. RESULTS: We observed a non-significant increase in the prevalence of binge drinking for every difference of 1 °C between municipalities of the same region. By alcohol type, a 1 °C increase in mean annual temperature across municipalities of the same region increased the prevalence of beer binge drinking in the past year by 0.9% (PR = 1.009, 95%CI 1.005, 1.013) among beer consumers and the prevalence of coolers' binge drinking by 3.0% (PR = 1.030, 95%CI 1.003, 1.057) in coolers consumers. We observed non-significant results for liquor binge drinking (PR = 1.047, 95%CI 0.994, 1.102) and wine binge drinking (PR = 1.047, 95% 0.944, 1.161). CONCLUSION: People living in municipalities with higher temperatures reported a higher beer binge drinking in Mexican cities. This could account for 196,000 cases of beer binge drinking in 2016. The context of each country needs to be considered when generalizing these findings, and they need to be further explored with longitudinal data as there might be implications for climate change. If our findings are confirmed given the forecasted rising temperatures, we could expect an increase in binge drinking and therefore, in the alcohol burden of disease.

A text message intervention aimed at nurturing peer outreach to help meet drinking limit goals: A remote pilot randomized trial in non-collegiate young adults.

OBJECTIVE: Scalable interventions attempting to nurture peer outreach to help young adults meet drinking limit goals remain under-developed. To address this gap, we developed ASPIRE, a text message intervention focused on coaching individuals to engage with close peers to assist them in meeting drinking limit goals. METHOD: Non-collegiate young adults who had reported one or more heavy drinking days in the preceding month and were at least contemplating change were recruited through social media. Participants were randomly assigned to one of three 6-week text message interventions: Control, Goal Support, or ASPIRE. All groups completed baseline assessments and received weekly text message assessments on Thursdays and Sundays. Control and ASPIRE groups were prompted to complete web-based outcome assessments at 6- and 12-weeks. RESULTS: We enrolled 92 young adults from 31 US states (65% female; 73% White). All groups had high text response rates but intervention usability was sub-optimal. Follow-up rates were 87% at 6-weeks and 79% at 12-weeks. Compared to Control, ASPIRE participants reported significantly more peer support and less peer pressure to drink. ASPIRE exhibited higher goal confidence compared to the Goal Support group. Using multiple imputation, there were no significant differences in drinking outcomes between groups. CONCLUSIONS: Preliminary findings from this pilot study suggest that a text message intervention focused on nurturing peer outreach to help meet drinking limit goals holds promise in altering peer support and pressure as well as boosting drinking limit goal confidence. Design improvements are needed to reduce alcohol consumption.

Converging Effects of Chronic Pain and Binge Alcohol Consumption on Anterior Insular Cortex Neurons Projecting to the Dorsolateral Striatum in Male Mice.

Chronic pain and alcohol use disorder (AUD) are highly comorbid, and patients with chronic pain are more likely to meet the criteria for AUD. Evidence suggests that both conditions alter similar brain pathways, yet this relationship remains poorly understood. Prior work shows that the anterior insular cortex (AIC) is involved in both chronic pain and AUD. However, circuit-specific changes elicited by the combination of pain and alcohol use remain understudied. The goal of this work was to elucidate the converging effects of binge alcohol consumption and chronic pain on AIC neurons that send projections to the dorsolateral striatum (DLS). Here, we used the Drinking-in-the-Dark (DID) paradigm to model binge-like alcohol drinking in mice that underwent spared nerve injury (SNI), after which whole-cell patch-clamp electrophysiological recordings were performed in acute brain slices to measure intrinsic and synaptic properties of AIC→DLS neurons. In male, but not female, mice, we found that SNI mice with no prior alcohol exposure consumed less alcohol compared with sham mice. Electrophysiological analyses showed that AIC→DLS neurons from SNI-alcohol male mice displayed increased neuronal excitability and increased frequency of miniature excitatory postsynaptic currents. However, mice exposed to alcohol prior to SNI consumed similar amounts of alcohol compared with sham mice following SNI. Together, our data suggest that the interaction of chronic pain and alcohol drinking have a direct effect on both intrinsic excitability and synaptic transmission onto AIC→DLS neurons in mice, which may be critical in understanding how chronic pain alters motivated behaviors associated with alcohol.

Differences in the relation of binge drinking and prescription drug misuse to suicide ideation and attempts between college-aged adults and adults above the age of 25: Findings from the 2015-2019 National Survey on Drug Use and Health (NSDUH).

OBJECTIVE: To clarify the role of age in risk associated with drug misuse and binge drinking, this study examines the differential relations of binge drinking and prescription drug misuse to risk of suicidal ideation and attempts in young adults of college age (18-24) compared to those above the age of 25. METHODS: We used data from the National Survey on Drug Use and Health (NSDUH) for the years 2015 through 2019 (N = 269,078). RESULTS: The study found that, for adults above college age, the presence of any past-month binge drinking was associated with a higher likelihood of past-year suicide ideation (b = 0.427, OR = 1.532, 95%CI [1.388, 1.692]) and attempts (b = 0.637, OR = 1.891, 95%CI [1.271, 2.813]) compared to college-aged adults. Similarly, past-month prescription drug misuse showed stronger associations with past-year suicide ideation (b = 0.831, OR = 2.297, 95%CI [1.952, 2.701]) and attempts (b = 0.539, OR = 1.715, 95%CI [1.264, 2.327]) in adults above college age. CONCLUSION: These findings highlight that binge drinking and prescription drug misuse appears to become more strongly associated with suicide ideation and attempts after adults age beyond young adulthood.

Co-action and changes in alcohol use during a smoking cessation attempt.

AIMS: Three smoking cessation studies (CARE, Break Free, Por Nuestra Salud [PNS]) were used to measure changes in average alcohol consumption, binge drinking and alcohol-related problems during a smoking cessation attempt and to explore co-action with smoking abstinence. DESIGN: CARE and PNS were longitudinal cohort cessation studies; Break Free was a two-arm randomized clinical trial. SETTING: Texas, USA. PARTICIPANTS: Participants were current smokers who were recruited from the community and received smoking cessation interventions. All participants received nicotine replacement therapy and smoking cessation counseling. CARE included 424 smokers (1/3 White, 1/3 African American and 1/3 Latino); Break Free included 399 African American smokers; PNS included 199 Spanish-speaking Mexican-American smokers. MEASUREMENTS: Weekly alcohol consumption was collected multiple times pre and post-quit, and binge drinking and alcohol-related problems were collected at baseline and 26 weeks post-quit. Analyses included only those who indicated current alcohol use. FINDINGS: Average alcohol consumption decreased from baseline to 26 weeks post-quit in CARE (F = 17.09, P < 0.001), Break Free (F = 12.08, P < 0.001) and PNS (F = 10.21, P < 0.001). Binge drinking decreased from baseline to 26 weeks post-quit in CARE (F = 3.94, P = 0.04) and Break Free (F = 10.41, P < 0.001) but not PNS. Alcohol-related problems decreased from baseline to 26 weeks post-quit in CARE (Chi-sq = 6.41, P = 0.010) and Break Free (Chi sq = 14.44, P = 0.001), but not PNS. CONCLUSIONS: Among current drinkers, alcohol use/problems appear to decrease during a smoking cessation attempt and remain low through 26 weeks after the quit attempt. Little evidence was found for co-action, with smoking abstainers and relapsers showing similar change in alcohol use/problems.

[Binge drinking in early adolescence : Results of the "Präventionsradar" from 2016 to 2023]. / Rauschtrinken in der frühen Adoleszenz : Ergebnisse des Präventionsradars von 2016 bis 2023.

INTRODUCTION: In Germany, no other psychotropic substance is consumed as often and in such large quantities during adolescence as alcohol. This work aims to examine trends in binge drinking in early adolescence from 2016 to 2023. METHOD: Based on seven waves of the "Präventionsradar," which is a school-based epidemiological study in lower secondary education, the lifetime as well as the 30-day prevalence of binge drinking (for girls 4, for boys 5 alcoholic drinks on one occasion) were determined for the period from 2016 to 2023 for 12- to 15-year-olds. RESULTS: The analyses were based on 44,713 questionnaires. The sex ratio was balanced (50% female), and the mean age was 13.8 years (SD = 1.02). From 2016 to 2023, lifetime prevalence of binge drinking increased significantly by 3.6 percentage points to 25.3% (95% confidence interval 24.1-26.5). The 30-day prevalence did not change statistically during the observation period and was 15.9% (95% CI 14.9-16.9) in 2023. Compared to the previous year, both lifetime prevalence (-2.5 percentage points) and 30-day prevalence of binge drinking (-3.5 percentage points) decreased significantly in the first year of the COVID-19 pandemic (2020/2021) and increased again in subsequent years. Systematic differences between the genders could not be found. DISCUSSION: The German Youth Protection Act does not allow legal access to alcohol for the age group under study. Against this background, it is worrying that every fourth adolescent already reports experiences of binge drinking. Consistent structural and behavioral prevention measures are necessary to curb the high prevalence of binge drinking in childhood and adolescence.

Early Drinking Onset and Subsequent Alcohol Use in Late Adolescence: a Longitudinal Study of Drinking Patterns.

PURPOSE: The age of drinking onset is a central concept for both policy and prevention of alcohol-related harm, yet evidence on the predictive value of the age of onset is lacking. This study compares alcohol outcomes of adolescents who started to drink early with those who started later, and tests if associations are moderated by other explanatory factors. METHODS: Data from a two-wave longitudinal prospective cohort survey with a Swedish nationwide sample of 4,018 adolescents aged 15/16 years at baseline (T1) and 17/18 years at follow-up (T2) were used. Outcome variables at T2 were Alcohol Use Disorders Identification Test (AUDIT)-C, risky drinking, and binge drinking monthly or more often. A vast number of explanatory factors at T1 were controlled for. RESULTS: Early drinking onset predicted later higher AUDIT-C scores (ß = 0.57, p value < .001), and higher probability of risky drinking (odds ratio = 1.95, 95% confidence interval = 1.56-2.44), and binge drinking (odds ratio = 1.38, confidence interval = 1.06-1.81), controlled for other explanatory factors. If binge drinking frequency at T1 was included, the associations remained for AUDIT-C and risky drinking, but not for binge drinking at T2. No significant interactions between early drinking onset and the explanatory factors were found. DISCUSSION: Early drinking onset predicts subsequent higher alcohol consumption in late adolescence. Adolescents who had an early drinking onset drank more after 2 years than their peers who started later. The age of drinking onset is an independent predictor of alcohol use outcomes, beyond the effect of age of binge drinking onset.

Proportion of At-Risk Alcohol Consumers According to the New French Guidelines: Cross-Sectional Weighted Analyses From the CONSTANCES Cohort.

Objective: To estimate the proportion of the participants of the French national population-based CONSTANCES cohort exceeding the new low-risk drinking guidelines according to sociodemographic and clinical factors. Methods: From 34,470 participants with follow-up data in 2019, among volunteers aged 18-69 years and invited to enroll in the CONSTANCES cohort in 2016 and 2017, weighted prevalence and odds ratios with 95% confidence intervals (CI) exceeding the guidelines using logistic regressions were presented stratified for age, gender, education, occupational grade, employment, income, marital status, pregnancy, work stress, depression, alcohol dependence, binge drinking, cannabis use, smoking status, e-cigarette use, cardiovascular diseases, and cancer. Results: The guidelines were exceeded more by men at 60.2% (95%CI: 59.3%-61.0%) than by women at 36.6% (95%CI: 35.9%-37.4%). Exceeding the guidelines increased with age, socioeconomic status, smoking, vaping, using cannabis, binge drinking, and alcohol dependence. Being depressed was associated with exceeding the guidelines in women. Even though pregnant women were less likely to exceed the guidelines, 7.6% (95%CI: 5.4%-10.6%) were at-risk drinkers. Conclusion: These findings highlight the need to implement effective prevention measures for at-risk alcohol use among the French population.

Prevalence and correlates of alcohol use among the elderly in the Eastern Caribbean Health Outcomes Research Network (ECHORN) cohort study.

BACKGROUND: Alcohol use is pervasive in the Caribbean; however, the prevalence and correlates of alcohol use and drinking problems in the elderly have not been extensively studied. METHODS: Data were obtained from the Eastern Caribbean Health Outcomes Research Network (ECHORN) Cohort Study, a cohort study of Caribbean people from Puerto Rico, Barbados, Trinidad, and Tobago, and the U.S. Virgin Islands, collected between 2013 and 2018 (baseline study sample, ages 60+, n = 811). Descriptive statistics were used to compare the differences in drinking status (current vs. former vs. never), alcohol problems (Cut-down, Annoyed, Guilty, and Eye-opener (CAGE) scale score ≥2 vs. <2), and binge drinking days (0 days vs. 1-2 days vs. ≥3 days) across sample characteristics. Logistic regression analyses estimated the association of these alcohol measures with sociodemographic (e.g., sex), psychological (depression), and cultural (e.g., religion) correlates. RESULTS: Thirty-six percent were 70 + years of age, 64 % were female, and 41 % had less than a high school education. Alcohol problems (≥2 CAGE score) was 21 %. Binge drinking ≥3 days was 30.6 %. Never attending religious services (vs. attending once a week or more) was associated with almost three times higher odds of alcohol problems (adjusted Odds Ratio: OR = 2.88, 95 % CI = 1.02, 8.15) four times higher odds of increasing binge drinking days (aOR = 4.04, 95 % CI = 1.11, 14.96). College education was protective against both the outcomes. CONCLUSION: We provide current estimates of alcohol problems among elderly Eastern Caribbean people. Among the sociodemographic, psychological, and cultural correlates examined, religious attendance was significant. Replicate longitudinal studies using DSM-5 alcohol dependence are recommended.

How Do Gain-Loss Frames and Cultural Arguments Persuade? Designing Effective Messages to Weaken College Students' Binge-Drinking Intentions.

To design effective health messages, this study investigates the effects of gain-loss framing and relevant moderating effects in the context of college students' alcohol use. Specifically, based on an online experiment, we tested the moderation effects of message-sidedness and binge-drinking behaviors using a mediation model in which the association between gain-loss framing and behavioral intentions is mediated by attitudes toward binge-drinking. Four hundred thirty-four Korean college students participated in this study. Hayes' PROCESS Macro for SPSS was employed for the analysis. The results show that loss-framing significantly increased participants' unfavorable attitudes toward binge-drinking in the one-sided message condition. Moreover, attitudes toward binge-drinking were more significantly associated with behavioral intentions to binge-drink among heavy drinkers than among non-heavy drinkers. Our findings suggest important theoretical and practical implications for the development of message-framing strategies in health campaigns designed to prevent college students' binge-drinking in collectivistic societies where the cultural meaning of drinking extends beyond the individual realm to the larger social context.

Estrogen signaling in the dorsal raphe regulates binge-like drinking in mice.

Estrogens promote binge alcohol drinking and contribute to sex differences in alcohol use disorder. However, the mechanisms are largely unknown. This study aims to test if estrogens act on 5-hydroxytryptamine neurons in the dorsal raphe nucleus (5-HTDRN) to promote binge drinking. We found that female mice drank more alcohol than male mice in chronic drinking in the dark (DID) tests. This sex difference was associated with distinct alterations in mRNA expression of estrogen receptor α (ERα) and 5-HT-related genes in the DRN, suggesting a potential role of estrogen/ERs/5-HT signaling. In supporting this view, 5-HTDRN neurons from naïve male mice had lower baseline firing activity but higher sensitivity to alcohol-induced excitation compared to 5-HTDRN neurons from naïve female mice. Notably, this higher sensitivity was blunted by 17ß-estradiol treatment in males, indicating an estrogen-dependent mechanism. We further showed that both ERα and ERß are expressed in 5-HTDRN neurons, whereas ERα agonist depolarizes and ERß agonist hyperpolarizes 5-HTDRN neurons. Notably, both treatments blocked the stimulatory effects of alcohol on 5-HTDRN neurons in males, even though they have antagonistic effects on the activity dynamics. These results suggest that ERs' inhibitory effects on ethanol-induced burst firing of 5-HTDRN neurons may contribute to higher levels of binge drinking in females. Consistently, chemogenetic activation of ERα- or ERß-expressing neurons in the DRN reduced binge alcohol drinking. These results support a model in which estrogens act on ERα/ß to prevent alcohol-induced activation of 5-HTDRN neurons, which in return leads to higher binge alcohol drinking.

Ethanol binge drinking exposure during adolescence displays long-lasting motor dysfunction related to cerebellar neurostructural damage even after long-term withdrawal in female Wistar rats.

Ethanol is one of the psychoactive substances most used by young individuals, usually in an intermittent and episodic manner, also called binge drinking. In the adolescent period, brain structures undergo neuromaturation, which increases the vulnerability to psychotropic substances. Our previous studies have revealed that ethanol binge drinking during adolescence elicits neurobehavioral alterations associated with brain damage. Thus, we explored the persistence of motor function impairment and cerebellum damage in the context of ethanol withdrawal periods (emerging adulthood and adult life) in adolescent female rats. Female Wistar rats (35 days old) received orally 4 cycles of ethanol (3.0 g/kg/day) or distilled water in 3 days on-4 days off paradigm (35th until 58th day of life). Motor behavioral tests (open field, grip strength, beam walking, and rotarod tests) and histological assays (Purkinje's cell density and NeuN-positive cells) were assessed on the 1-, 30-, and 60-days of binge alcohol exposure withdrawal. Our findings demonstrate that the adolescent binge drinking exposure paradigm induced cerebellar cell loss in all stages evaluated, measured through the reduction of Purkinje's cell density and granular layer neurons. The cerebellar tissue alterations were accompanied by behavioral impairments. In the early withdrawal, the reduction of spontaneous movement, incoordination, and unbalance was seen. However, the grip strength reduction was found at long-term withdrawal (60 days of abstinence). The cerebellum morphological changes and the motor alterations persisted until adulthood. These data suggest that binge drinking exposure during adolescence causes motor function impairment associated with cerebellum damage, even following a prolonged withdrawal, in adult life.