Adolescent Alcohol Research Articles

Psychological outpatient follow-up after hospitalization for adolescent acute alcohol intoxication.

The findings of this study demonstrate that a preventive program following acute alcohol intoxication contributes to the reduction of adolescent alcohol use and associated risk-taking behaviours. • Earlier studies showed that adolescents with problematic alcohol use reported reduced alcohol consumption and fewer alcohol-related problems after participating in a motivational interviewing intervention compared to standard care. • During the follow-up assessment of adolescents with acute alcohol intoxication it is possible to signalize mental disorders and to determine whether the patient requires referral to specialized mental healthcare. • These findings suggest that the preventive program had a short-term impact in reducing alcohol consumption among adolescents with acute alcohol intoxication, as well as a long-term impact in reducing binge-drinking behaviours. • The program's success in mitigating binge-drinking behaviours aligns with its goals of promoting safer drinking habits among adolescents.

An integrated alcohol and suicide intervention for adolescents in inpatient psychiatric treatment.

Despite the bidirectional relationship between alcohol use and STB, the two issues are often treated separately in adolescent inpatient psychiatric hospitals, highlighting the need for brief interventions that address both alcohol use and STB in an integrated fashion. This study tested the feasibility, acceptability, and preliminary effectiveness of a brief integrated Alcohol and Suicide Intervention for Suicidal Teens (iASIST) with a post-discharge mHealth booster for adolescents in inpatient psychiatric treatment. We conducted an RCT of iASIST relative to an attention-matched comparison condition with adolescents hospitalized following STB (N = 40). iASIST demonstrated feasibility and acceptability and mixed models indicated that both groups had significant decreases in substance use over the 3-month follow-up, but post-intervention group differences were not significant. In terms of cannabis use, however, iASIST participants significantly improved over time. Intervention group participants showed a significant decrease in suicide plans from baseline to follow-up, which was not the case for control group participants. Study findings suggest a larger RCT is warranted to test the effectiveness of the iASIST intervention. iASIST shows promise in its ability to target the public health problems of alcohol use and STB in an integrated fashion with a high-risk adolescent population receiving acute psychiatric care.

The Burden of Alcohol and Substance Use Disorders in Adolescents and Young Adults

The Burden of Alcohol and Substance Use Disorders in Adolescents and Young Adults

Parental Monitoring and Its Association With Alcohol, Tobacco Cigarettes, and Cannabis Initiation in the United States Adolescent Population

PurposeLimiting time with friends (LTWF), a facet of parental monitoring, may be protective for newly incident adolescent alcohol, tobacco cigarette, and cannabis use. MethodsWe extended epidemiological evidence based on estimates from nationally representative samples of US adolescents aged 12–17 years, across 18 years of independent samples of the National Survey on Drug Use and Health (2002–2019). We estimated the prevalence of always LTWF, and odds ratios examining incident alcohol, tobacco cigarette, and cannabis use by LTWF within age and cohort. ResultsThe prevalence of always LTWF decreased with older age within study year and cohort. The odds of alcohol initiation were lower among youth reporting their parents were always LTWF. The odds of tobacco cigarette and cannabis initiation were lower among younger youth reporting their parents were always LTWF. DiscussionFuture research is needed to fully understand the influence of LTWF on incident substance use, particularly for older adolescents.

Preadolescent individual, familial, and social risk factors associated with longitudinal patterns of adolescent alcohol, cannabis, and other illicit drug use in a population-representative cohort.

The aim of this exploratory study was to identify developmental patterns of adolescent concurrent alcohol, cannabis, and other illicit drug use and their preadolescent individual, familial, and social risk factors in a population-representative cohort from the province of Quebec, Canada (N = 1,593; 48.4% male). Age 12-17 years self-reports of alcohol, cannabis, and other illicit drug use were collected. Latent growth modeling was used to analyze developmental patterns of single- or polysubstance use (SU/PSU), and multinomial regression examined their association with risk factors assessed at age 10-12 years. Five developmental patterns were revealed, including nonusers (12.8% sample) and four classes reflecting different levels of SU/PSU (5.8%-37.5%), varying in severity based on onset, frequency, and type of substances used. Boys and girls were similarly represented throughout SU/PSU patterns. In comparisons with nonusers, several preadolescent risk factors were associated with increasing severity of SU/PSU. Possibly indexing fearlessness/disinhibition, low internalizing symptoms were common to all adolescent users. An earlier onset of substance use and increasing use of substances throughout adolescence were linked with having deviant peers for all user classes but later-onset users. Preadolescents manifesting externalizing problems and exposed to family adversity in addition to the above risk factors showed the earliest onset and most frequent adolescent SU/PSU, especially those also exposed to less appropriate parenting. Consistent with the developmental model of substance use, the nature, number, and severity of preadolescent risk factors distinguished between the type and severity of SU/PSU patterns in adolescence and call for a consistent strategy of universal, selective, and indicated preventive interventions. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

An investigation of multimodal predictors of adolescent alcohol initiation

BackgroundEarly alcohol initiation is associated with negative, alcohol-related outcomes. While previous work identifies numerous risk factors for early use, the relative contributions of known predictors remains understudied. The current project addresses this gap by 1) prospectively predicting early alcohol initiation using measures of inhibition control, reward sensitivity, and contextual risk factors and 2) interrogating the relative importance of each domain. MethodThis study leverages multimodal data from substance-naïve youth enrolled in the Adolescent Brain Cognitive Development (ABCD) Study® (n=11,694). Early initiation was defined as consuming a full standard drink containing alcohol prior to age 16. Propensity scores were used to match alcohol initiators (n=348) with demographically similar non-initiators at a 1:2 ratio (n=696). Independent logistic regressions were conducted for each domain followed by additive, hierarchical models. ResultsThe model of contextual factors (pseudo-R2=0.086, AUC=0.67) outperformed inhibition control (pseudo-R2=0.021, AUC=0.58) and reward sensitivity measures (pseudo-R2=0.020, AUC=0.59). The hierarchical model containing all measures (pseudo-R2=0.106, AUC=0.69) did not significantly improve the model of contextual factors alone (p>0.05). Examples of significant predictors (p<0.05) include externalizing behaviors, number of substances known, and non-religious alcohol sipping. ConclusionContextual risk factors were the strongest predictors of early alcohol use; however, more work is needed to understand the causal nature of this relationship. Measures of inhibition control and reward sensitivity were not adequate in distinguishing initiators from non-initiators. These findings add to a body of evidence that contextual factors play a major role in alcohol initiation while highlighting specific predictor variables that could inform youth alcohol prevention.

Adolescent alcohol drinking and cannabis use: Longitudinal, and cohort analysis of high school students in Australia

Aims: The final year of high school is a challenging phase, during which substance use is common. We conducted longitudinal and cohort comparisons on the levels of alcohol and cannabis use among final year (Year 12) high school students compared to the previous year. Design: Longitudinal and cohort analyses of self-reported survey data. Setting: Ten independent schools across South-East Queensland, Australia. Participants: Year 12 students in 2020 (n = 1024) were compared (a) longitudinally with themselves in Year 11; and (b) to the 2019 Year 12 cohort (n = 632). Measures: Self-reported alcohol and cannabis use. Analyses adjusted for socio-demographic, parental, and schooling variables. Findings: Longitudinally, Year 12 students of 2020 had higher odds of having six or more drinks per occasion, monthly or more often, and reporting lifetime cannabis use, compared to themselves in 2019. However, they were not more likely to drink alcohol weekly or more often in 2020 versus 2019. Compared to the 2019 cohort, the 2020 cohort had higher odds of drinking weekly or more often, having six or more drinks per occasion monthly, and reporting lifetime cannabis use. Conclusions: The 2020 cohort of Year 12 adolescents were more likely to engage in heavy drinking and cannabis use, compared to themselves the previous year, and compared to the previous cohort. Greater alcohol consumption and likelihood of cannabis use among the 2020 cohort might be explained by increased age and impacts of the COVID-19 pandemic. Future research to monitor if this is a continuing trend is warranted.

Examining the link between age of alcohol initiation, adolescent alcohol use and adult substance use

Abstract Background Understanding the relationship between adolescent alcohol use and adult substance use is important for prevention programmes. Existing evidence presents divergent findings and potential mechanisms are debated. Methods We estimated associations between the age of alcohol initiation and alcohol use at age 17 and substance use at age 20 in a nationally representative cohort (n = 4554). Weighted logistic regression models were fitted using Generalised Estimating Equations in multiply imputed and complete case data. Results Our analysis identified that 27% of participants reported first alcohol use at ≤ 14 years old, with 37% engaging in risky alcohol use by age 17. At age 20, 14% reported hazardous alcohol use, while 38% used tobacco, 24% cannabis, and 28% other drugs. The age at which alcohol was initiated and risky alcohol use at 17 years old were both strongly associated with alcohol, tobacco, cannabis and other illicit drug use at 20 years old. Sequential change in effect estimates coupled with non-overlapping confidence intervals suggest a dose-response relationship between age of alcohol initiation and tobacco and other drug use at age 20. Conclusions First use of alcohol at 14 or younger was common. Earlier alcohol initiation and risky alcohol use are each associated with substantially elevated risk for substance use at 20 years old even after accounting for common liability factors. Acknowledgement: Growing Up in Ireland (GUI) is funded by the Department of Children, Equality, Disability, Integration and Youth (DCEDIY). It is managed by DCEDIY in association with the Central Statistics Office (CSO). Results in this report are based on analyses of data from Research Microdata Files provided by the CSO. Neither the CSO nor DCEDIY take any responsibility for the views expressed or the outputs generated from these analyses. Key messages • Delaying alcohol initiation and preventing risky alcohol use during adolescence may reduce levels of substance use in young adults. • Self-reported early use of alcohol remains common.

Supply of Alcohol in Early Childhood Leads to Higher Rates of Drinking in Adolescence

Abstract Background Adolescents often experience their first encounter with alcohol at home, provided by parents who perceive it as a means of safeguarding their children against later alcohol-related issues. However, research shows that parental supply of alcohol is a risk factor for adolescent drinking. Notably, existing studies solely focused on parental supply during adolescence, neglecting the prospective evaluation of parental alcohol provision during early childhood on later alcohol use. Methods The data came from the Czech part of the European Longitudinal Study of Pregnancy and Childhood (ELSPAC), a longitudinal birth cohort study (N = 5,777). Mothers reported on the frequency of offering alcohol to children when children were 3, 5, 7, and 11 years old. The outcome was adolescent alcohol use at ages 15 and 18, reported by adolescents, mothers, and pediatricians. Control variables included sex, maternal education, family structure, and parental alcohol consumption. Results Three classes of children were identified based on parental alcohol supply: abstainers (75.5% of sample), infrequent sippers (16.2%), and frequent sippers (8.3%). Parental drinking increased the risk of both infrequent and frequent sipping. These classes were entered into two structural models (age 15 and age 18 alcohol use modeled as latent factors), alongside covariates. Compared to abstainer class, infrequent and frequent childhood sippers exhibited significantly higher alcohol consumption at age 15 (β = .21, p &amp;lt; .001; β = .25, p &amp;lt; .001, respectively) and age 18 (β = .11, p &amp;lt; .05; β = .24, p &amp;lt; .001, respectively). Conclusions This study represents the first prospective investigation quantifying early childhood alcohol exposure and its subsequent association with adolescent alcohol consumption. Findings emphasize the influence of family dynamics on alcohol behaviors, underscoring the necessity for targeted preventive measures, particularly within families with higher parental alcohol consumption. Key messages • Offering alcohol to children at ages 3-11, even infrequently, significantly increases the risk of more frequent drinking at ages 15 and 18, compared to those with no early exposure. • Parents who drink are more likely to have children who sip alcohol early, leading to higher alcohol consumption in adolescence. Prevention efforts should focus on family habits and early education.

Predictors and outcomes of adolescent alcohol and drug use: a scoping review

Abstract Background Adolescence is a pivotal life stage marked by educational advancement, entry into the workforce and formation of lasting relationships. Globally, adolescence is also the peak period during which individuals first engage in alcohol and/or drug consumption. This scoping review aimed to summarize existing longitudinal research on factors and outcomes related to adolescent substance use to identify gaps in existing evidence. Methods A scoping review was conducted in accordance with the PRISMA extension for scoping reviews. A systematic literature search was conducted on PubMed. Additional studies were identified through hand-searching key reference lists and Google Scholar searches. A narrative synthesis was completed. Results 123 studies were included; 12 reviews and 111 cohort studies. 60% of cohort studies originated from North America, 29% Europe, 7% Australia/New Zealand, 2% South America and 2% Asia. Factors consistently associated with increased risk of ASU include male sex, increasing age, externalizing disorders, adverse childhood experiences and peer or parental substance use. Few studies considered wider community or neighbourhood factors. Early initiation and higher frequency of adolescent drug use were predictive of later-life substance use patterns, education derailment, contact with the justice system and mental health disorders. Conclusions The body of longitudinal evidence on adolescent substance use is rapidly expanding yet significant research gaps exist. Rising levels of cocaine use and its substantial health impacts motivate further research on all potentially important factors associated with cocaine use to guide interventions for prevention and treatment. Key messages • There are important gaps in existing research on adolescent substance use. • These include neighbourhood influences and factors associated with initiation of illicit drugs other than cannabis.

5.Y.2. Alcohol intoxication among adolescents in Italy, Belgium and The Netherlands

Abstract Excessive drinking behavior poses a significant risk to the health of adolescents and contributes to high social and health costs. It is also well-documented that engaging in risky drinking behavior at a young age increases the likelihood of developing alcohol use disorders and other mental health disorders later in life. Therefore, the timely development of adequate interventions to prevent and reduce such behavior is an important public health task. The initial step here is to gather comprehensive data on the phenomenon. Studying alcohol intoxication data among adolescents is an important source in this context. In the Netherlands, data on alcohol intoxication in adolescents have been routinely collected for several years, leading to a successful transmural framework aimed at supporting these young individuals and their parents. As countries are at varying stages in addressing this issue, the objective of this workshop is to facilitate mutual learning about effective prevention initiatives targeting problematic alcohol use in young people. The workshop will feature presentations from four studies representing three countries: Italy, Belgium, and the Netherlands. Allegra Ferrari from Italy will discuss alcohol-related emergencies among adolescents admitted to an emergency department in Genoa, emphasizing the importance of urgent interventions to mitigate adolescent alcohol use. Hanna van Roozendaal from Belgium will present data from both retrospective and prospective studies on adolescents with acute alcohol intoxication in Antwerp hospitals, exploring the feasibility of follow-up interventions. Louise Pigeaud from the Netherlands will share data from a cohort of individuals under 18 years presented with acute alcohol intoxication symptoms at an emergency department between 2015-2023 to monitor trends in admission characteristics. Finally, Guido van Hal will focus more in depth on the differences and similarities in adolescents accessing emergency care for acute alcohol intoxication in Italy, Belgium and The Netherlands. The workshop will conclude with an open discussion on topics such as the necessary data to be registered for minors with acute alcohol intoxication, the most effective methods for preventing/reducing alcohol intoxication in these age groups, and the potential transferability of the successful Dutch transmural framework to other countries. Key messages • Acute alcohol intoxication and problematic alcohol use in minors can lead to significant alcohol-related issues in adulthood. • Collecting and analyzing high-quality data can facilitate the development of interventions aimed at reducing and preventing alcohol-related issues in adolescents.

Alcohol related emergencies among adolescents admitted in a referral acute-care center for adults in Genoa, northwest Italy

Abstract Background As a result of underage drinking, adolescents have an increased risk of physical, mental, emotional, and social harm. Methods In order to assess the emergencies for alcohol use, data of the emergency department (ED) of San Martino Hospital - the referral acute-care center for adults in Genoa, Northwest Italy - was analyzed retrospectively. 330 records of 320 adolescents visiting the ED between 2014 and 2023 were considered. Results The median age of access was 16 (IQR 2), 54.8% were males, 17.4% had foreign nationalities, and the average blood alcohol concentration (BAC) was 1.8 g/L (SD 0.7), with 14.7% testing positive for other substances (6.1% benzodiazepines and 11.2% other drugs). 16.8%, 46.6% and 36.6% were assigned an emergency, urgent, and not-urgent acuity code. 2.8% had a repeated episode, 3.4% had to be removed for inappropriate behavior, 7.8% left spontaneously, 13.1% were hospitalized for additional care (5.5% in the Psychiatry ward). The average length of stay was 1.24 days (SD 5.86). Multivariable logistic regression showed that higher age, an emergency code and the use of other substances were positively associated with hospitalization [ORs 1.74 (95%CI 1.1-2.7), p 0.01; 7.1 (95%CI 2.2-22.4) p &amp;lt; 0.001; and 15.6 (95%CI 6.8-35.6) p &amp;lt; 0.001, respectively]. Admission in Psychiatry, in particular, was strongly associated with the use of other substances [OR 11.8 (95%CI 3.8-36.6), p &amp;lt; 0.001]. Multivariable linear regression showed that, in comparison with other access reasons, accidents and decreased consciousness were associated with higher BAC [beta 0.6 (95%CI 0.1-1.1), p 0.01; beta 0.8 (95%CI 0.3-1.2) p &amp;lt; 0.001]. Length of stay, however, was associated with lower BAC [beta -0.2 (95%CI -0.3 -0.01), p 0.04]. Conclusions In Italy, binge drinking affects 120,000 adolescents aged 11-17. Our findings highlight the harm of this practice and support the need for prompt interventions to reduce the onset and prevalence of adolescent alcohol use.

Supplemental Material for Preadolescent Individual, Familial, and Social Risk Factors Associated With Longitudinal Patterns of Adolescent Alcohol, Cannabis, and Other Illicit Drug Use in a Population-Representative Cohort

Supplemental Material for Preadolescent Individual, Familial, and Social Risk Factors Associated With Longitudinal Patterns of Adolescent Alcohol, Cannabis, and Other Illicit Drug Use in a Population-Representative Cohort

Enhanced Fear Extinction Through Infralimbic Perineuronal Net Digestion: The Modulatory Role of Adolescent Alcohol Exposure.

Perineuronal nets (PNNs) are specialized components of the extracellular matrix that play a critical role in learning and memory. In a Pavlovian fear conditioning paradigm, degradation of PNNs affects the formation and storage of fear memories. This study examined the impact of adolescent intermittent ethanol (AIE) exposure by vapor inhalation on the expression of PNNs in the adult rat prelimbic (PrL) and infralimbic (IfL) subregions of the medial prefrontal cortex. Results indicated that following AIE, the total number of PNN positive cells in the PrL cortex increased in layer II/III but did not change in layer V. Conversely, in the IfL cortex, the number of PNN positive cells decreased in layer V, with no change in layer II/III. In addition, the intensity of PNN staining was significantly altered by AIE exposure, which narrowed the distribution of signal intensity, reducing the number of high and low intensity PNNs. Given these changes in PNNs, the next experiment assessed the effects of AIE and PNN digestion on extinction of a conditioned fear memory. In Air control rats, digestion of PNNs by bilateral infusion of Chondroitinase ABC (ChABC) into the IfL cortex enhanced fear extinction and reduced contextual fear renewal. In contrast, both fear extinction learning and contextual fear renewal remained unchanged following PNN digestion in AIE exposed rats. These results highlight the sensitivity of prefrontal PNNs to adolescent alcohol exposure and suggest that ChABC-induced plasticity is reduced in the IfL cortex following AIE exposure.

Sibling socialization of alcohol use during adolescence: An integrated model of sibling influence processes.

Research demonstrates that siblings, especially older siblings, make unique contributions to adolescents' substance use above and beyond shared genetics and shared parenting. Older siblings' influences on younger adolescent siblings' alcohol use operate through both direct and indirect pathways. Using three waves of longitudinal data, the present study tested an integrated model of sibling influence processes focused on the linkages between older adolescent siblings' earlier alcohol use and younger adolescent siblings' later alcohol use. Longitudinal study using data collected from families on three occasions: Time 1 (March 2019-February 2020), Time 2 (July 2020-February 2021) and Time 3 (November 2021-February 2022) via online surveys. Families resided in five midwestern states in the US (Illinois, Indiana, Ohio, Pennsylvania and Wisconsin). Participants included two adolescent-aged siblings and one parent from 682 families (n = 2046 persons). Alcohol use by adolescents and parents was assessed at Time 1; younger siblings' social alcohol expectancies and perceptions of modeling were measured at Time 2; and younger siblings' alcohol use was measured at Time 3. Older siblings' earlier alcohol use predicted younger siblings' later drinking both directly [b = 0.15, standard error (SE) = 0.04, β = 0.17, P < 0.001] and indirectly through younger siblings' social alcohol expectancies [δ = 0.02, SE = 0.008, 95% confidence interval (CI) = 0.003, 0.03]. The direct (δ = -0.14, SE = 0.07, 95% CI = -0.27, -0.01) and indirect (δ = 0.03, SE = 0.02, 95% CI = 0.0001, 0.06) links were further moderated by younger siblings' reports of sibling modeling, but not by gender composition of the sibling dyad or the interaction of modeling and gender composition. Older siblings' alcohol use appears to influence younger siblings' later alcohol use directly, as well as indirectly through younger siblings' expectancies about alcohol. The global context of the sibling relationship, in this case sibling modeling, may further amplify or dampen these pathways of influence.

To study impact of drug abuse in adolescence

Adolescent drug usage can lead to a variety of outcomes that are different from those associated with adult drug use. Alcohol is a common illicit substance in youth, and the molecular mechanisms behind alcohol-induced neuro inflammation, brain injury, and behavioural dysfunction caused by ethanol are not fully understood. In the adult brain, alcoholism is associated with a higher chance of neuropsychiatric diseases. Adolescent alcohol use can cause long-lasting modifications to the control of cytokines and the sensitivity of the hypothalamic-pituitary-adrenal (HPA) axis, which can impact neuropathology and behaviour long into adulthood... Synthetic androgens used for muscle and strength gain, especially in adolescence, are called alcoholic androgenic steroids (AAS). Adult neuropathology and alcoholism can be prevented and treated using AAS, an anabolic steroid.

Adolescent alcohol consumption predicted by differences in electrophysiological functional connectivity and neuroanatomy.

Alcohol consumption during adolescence has been associated with neuroanatomical abnormalities and the appearance of future disorders. However, the latest advances in this field point to the existence of risk profiles which may lead to some individuals into an early consumption. To date, some studies have established predictive models of consumption based on sociodemographic, behavioral, and anatomical-functional variables using MRI. However, the neuroimaging variables employed are usually restricted to local and hemodynamic phenomena. Given the potential of connectome approaches, and the high temporal dynamics of electrophysiology, we decided to explore the relationship between future alcohol consumption and electrophysiological connectivity measured by MEG in a cohort of 83 individuals aged 14 to 16. As a result, we found a positive correlation between alcohol consumption and the functional connectivity in frontal, parietal, and frontoparietal connections. Once this relationship was described, multivariate linear regression analyses were used to evaluate the predictive capacity of functional connectivity in conjunction with other neuroanatomical and behavioral variables described in the literature. Finally, the multivariate linear regression analysis determined the importance of anatomical and functional variables in the prediction of alcohol consumption but failed to find associations with impulsivity, sensation seeking, and executive function scales. In conclusion, the predictive traits obtained in these models were closely associated with changes occurring during adolescence, suggesting the existence of different paths in neurodevelopment that have the potential to influence adolescents' relationship with alcohol consumption.

Examining associations between brain morphology in late childhood and early alcohol or tobacco use initiation in adolescence: findings from a large prospective cohort

A prominent challenge in understanding neural consequences of substance use involves disentangling predispositional risk factors from resulting consequences of substance use. Existing literature has identified pre-existing brain variations as vulnerability markers for substance use throughout adolescence. As early initiation of use is an important predictor for later substance use problems, we examined whether pre-existing brain variations are associated with early initiation of use.In the Generation R Study, a prospective population-based cohort, brain morphology (gray matter volume, cortical thickness and surface area) was assessed at ages 10 and 14 using neuroimaging. In the second wave, participants reported on alcohol and tobacco use initiation. From a base study population (N = 3019), we examined the longitudinal (N = 2218) and cross-sectional (N = 1817) association between brain morphology of frontolimbic regions of interest known to be associated with substance use risk, and very early (age < 13) alcohol/tobacco use initiation. Additionally, longitudinal and cross-sectional associations were examined with a brain surface-based approach. Models were adjusted for age at neuroimaging, sex and relevant sociodemographic factors.No associations were found between brain morphology (ages 10 and 14) and early alcohol/tobacco use initiation (<13 years). Sex-specific analyses suggested a cross-sectional association between smaller brain volume and early initiated tobacco use in girls. Our findings are important for interpreting studies examining neural consequences of substance use in the general population. Future longitudinal studies are needed to specify whether these findings can be extended to initiation and continuation of alcohol/tobacco use in later stages of adolescence.

BNST CRF receptor type 1 modulates mechanical hypersensitivity induced by adolescent alcohol exposure in adult female mice.

Alcohol exposure during adolescence has been linked to long-lasting behavioral consequences, contributing to the development of alcohol use disorder. Negative affect and chronic pain during alcohol withdrawal are critical factors influencing problematic alcohol use and relapse. Our previous research demonstrated that adolescent intermittent ethanol (AIE) vapor exposure elicits sex-specific negative affect-like behavior in adult mice following stress exposure. Additionally, AIE induces persistent mechanical hypersensitivity, which is accompanied by increased activation of corticotropin-releasing factor receptor type 1 (CRFR1) neurons in the dorsolateral bed nucleus of the stria terminalis (dlBNST). This study extends previous work by investigating plasma corticosterone levels and CRFR1 protein expression in the dlBNST following restraint stress exposure in adult mice with an AIE history. We also aim to explore the role of dlBNST CRFR1 signaling in mediating negative affect-like behavior and mechanical hypersensitivity. Female mice exhibited elevated plasma corticosterone levels compared to males following restraint stress. Moreover, females with AIE history showed higher expression of CRFR1 protein in the dlBNST compared to air controls. Antagonism of CRFR1 in the dlBNST blocked AIE-induced mechanical hypersensitivity in adult females but did not affect stress-induced negative affect-like behavior. In alcohol-naïve females, intra-dlBNST administration of a CRFR1 agonist induced mechanical hypersensitivity. These findings provide new insights into the neurobiological mechanisms underlying stress-induced negative affect and pain-related behavior, both influenced by a history of adolescent alcohol exposure. The results suggest that CRFR1 antagonists warrant further investigation for their potential in addressing alcohol-related chronic pain.

Sex-dependent effects of acute stress and alcohol exposure during adolescence on mRNA expression of brain signaling systems involved in reward and stress responses in young adult rats

BackgroundAdolescent stress and alcohol exposure increase the risk of maladaptive behaviors and mental disorders in adulthood, with distinct sex-specific differences. Understanding the mechanisms underlying these early events is crucial for developing targeted prevention and treatment strategies.MethodsMale and female Wistar rats were exposed to acute restraint stress and intermittent alcohol during adolescence. We assessed lasting effects on plasma corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels, and mRNA expression of genes related to corticotropin releasing hormone (CRH), neuropeptide Y (NPY), corticoid, opioid, and arginine vasopressin systems in the amygdala and hypothalamus.ResultsThe main findings are as follows: (1) blood alcohol concentrations (BAC) increased after the final alcohol administration, but stressed males had lower BAC than non-stressed males; (2) Males gained significantly more weight than females; (3) Stressed females showed higher ACTH levels than non-stressed females, with no changes in males; (4) Stress increased CORT levels in males, while stressed, alcohol-treated females had lower CORT levels than non-stressed females; (5) CRH: Females had lower Crhr1 levels in the amygdala, while alcohol reduced Crhr2 levels in males but not females. Significant interactions among sex, stress, and alcohol were found in the hypothalamus, with distinct patterns between sexes; (6) NPY: In the amygdala, stress reduced Npy and Npy1r levels in males but increased them in females. Alcohol decreased Npy2r levels in males, with varied effects in females. Similar sex-specific patterns were observed in the hypothalamus; (7) Corticoid system: Stress and alcohol had complex, sex-dependent effects on Pomc, Nr3c1, and Nr3c2 in both brain regions; (8) Opioid receptors: Stress and alcohol blunted the elevated expression of Oprm1, Oprd1, and Oprk1 in the amygdala of males and the hypothalamus of females; (8) Vasopressin: Stress and alcohol interacted significantly to affect Avp and Avpr1a expression in the amygdala, with stronger effects in females. In the hypothalamus, alcohol increased Avp levels in females.ConclusionsThis study demonstrates that adolescent acute stress and alcohol exposure induce lasting, sex-specific alterations in systems involved in reward and stress responses. These findings emphasize the importance of considering sex differences in the prevention and management of HPA dysfunction and psychiatric disorders.