Neural reward sensitivity and longitudinal patterns of alcohol and cannabis use in college-aged youth.

Overconsumption of alcohol and energy-dense, palatable foods commonly co-occur, and are both characterised by overlapping impairments in reward circuitry function. Elevated consumption of energy-dense foods may increase risk of alcohol binging through sensitising brain responsivity to alcohol rewards, thereby increasing the motivating effects of alcohol consumption. However, the acute effects of dietary intake on brain responses to alcohol in humans remains unclear. Therefore, the current study aimed to understand how intake of energy-dense foods may prime proximate brain responses to alcohol rewards. Thirty-four healthy adults completed a single test session where they were randomly allocated to receive either a high energy (N=18) or lower energy (N=16) breakfast prior to completing the Beer Incentive Delay (BID) task, which measures blood oxygen level dependent (BOLD) response to the anticipation, outcome notification, and consumption of beer rewards. The BID elicited hypothesized activation within reward networks during the anticipation and receipt of beer compared to the control beverage. However, no group activation differences were found. Self-report levels of saturated-fat intake were associated with attenuated putamen response during outcome notification of beer rewards in both groups. Behaviourally, high energy breakfast consumption was associated with faster responding to beer rewards. These findings suggest the intake of high fat foods may be linked to acute alterations in alcohol sensitivity, highlighting a potential mechanism explaining elevated risk of elevated alcohol consumption in those who regularly consume palatable, energy-dense foods.

Monitoring the surroundings relies on aerospace sensors to provide immediate information on the purity of the air, temperature, humidity, and atmospheric pressure. Aerospace and space mission environmental monitoring essentials sophisticated humidity sensors for aerospace. Humidity sensor efficiency, reliability of data, and future expansion are the challenges. Selection of polymer-based nanocomposites yields innovative humidity sensor hybrid nanocomposites with sensitive, stable, robust, low cost, simple to handle, and real-time features. The research field lacks knowledge regarding the effects of these metal oxides (MOs) on essential polymer composition and humidity sensitivity, despite their ability to increase active sides and surface area for humidity detection. A theoretical investigation was conducted to examine the impact of different MOs on the sensitivity, stability, and electrical characteristics of a Polyvinyl Alcohol (PVA) matrix. The interaction among various MOs and the PVA matrix produces the formation of new active chemical groups, thereby improving the sensitivity and reactivity of PVA. The observed reactivity is associated with the elevated surface energy exhibited by PVA, with the optimal modification observed being the incorporation of Zinc oxide (ZnO) nanofiller. Fabricated sensors with PVA-ZnO based have potential for advancement by integrating recent additional ingredients particularly graphene (G), which may create innovative composite PVA-ZnO-G to immediately enhance the surface characteristics of reactivity, thereby improving humidity detection sensitivity. The PVA-ZnO-G hybrid nanocomposite was synthesized, and its surface and intermolecular characteristics were studied, along with reactivity, hardness, softness, sensitivity and selectivity, were analyzed for humidity sensing. When evaluating the PVA-ZnO-5H2O complex against the PVA-ZnO-G -5H2O complex, it is evident that the latter exhibits superior electronic characteristics. Notably, it possesses a larger dipole moment of 21.0848 Debye, a reduced band gap of 0.503 eV, and a significantly more favorable adsorption energy of -0.7592 eV. The corresponding increase in the equilibrium constant (log K = 12.8380) further indicates that PVA-ZnO-G is thermodynamically practical and exhibit enhanced stability and sensitivity. In particular, the mechanical and thermal properties were enhanced, and the electrical environment was fundamentally altered to facilitate increased H2O interaction because of the hybridization of ZnO and the incorporation of G into the matrix.

Effects of predator odor stress on alcohol-induced conditioned taste aversion and lateral habenula cFos expression in rats.

Background:Studies in humans and animal models have documented relationships between initial sensitivity to alcohol and alcohol drinking behavior.Prior expression profiling studies of C57BL/6J and DBA/2J mice and rhesus macaques within the prefrontal cortex (PFC) have shown variation in myelin gene expression may be linked with alcohol sensitivity and consumption.Methods:Combining gene expression studies from human and mouse PFC, we identified a cross-species gene network enriched for myelin-associated genes. Since myelin expression is correlated to alcohol sensitivity and alcohol drinking behavior, we hypothesized basal levels of PFC myelin gene expression may be a genomic determinant for these behavioral responses. Using an animal model of CNS demyelination, and localized knock down of N-myc downstream regulated gene 1 (Ndrg1), we measured effects of cortical myelin reduction on initial alcohol sensitivity and drinking behavior.Results:Reducing myelin-related gene expression significantly altered sensitivity to alcohol and decreased alcohol consumption. Mouse genetic-based studies identified Ndrg1 as a putative quantitative trait gene for sedative-hypnotic responses to alcohol. Site-specific injections of shNdrg1 lentivirus into PFC led to a significant decrease in NDRG1 expression, causing increased alcohol behavioral sensitivity and reduced preference for high concentrations of alcohol.Conclusion:Myelin is an important biological component underlying CNS disorders. Our studies demonstrate the role of a novel candidate gene (Ndrg1), and myelin-associated gene expression, as an important factor modulating initial sensitivity to alcohol and alcohol consumption. Differences in the expression of myelin-related genes, including Ndrg1, may serve as future therapeutic targets for the treatment of alcohol use disorders.

Individuals with a genetically driven impairment in acetaldehyde metabolism have acute alcohol sensitivity and experience a range of heightened physiological responses, including skin flushing after consuming alcohol. Some individuals consume histamine receptor antagonists (antihistamines) to block the skin flushing response. However, our knowledge of the effects of antihistamines on the physiological responses of alcohol is poor. The purpose of this scoping review was to evaluate the current evidence of the effects of antihistamines on the physiological effects of alcohol among individuals with acute alcohol sensitivity and identify gaps in this literature. A scoping review was conducted to identify studies prior to March 2024 that administered alcohol and antihistamines to individuals with natural or induced alcohol sensitivity and examined the following physiological responses: skin flushing, heart rate, blood pressure, and skin temperature. Seven experimental studies were identified. Antihistamines showed some evidence in reducing alcohol-induced skin flushing, which was associated with a reduction in skin temperature. Antihistamines showed inconsistent effects on alcohol-associated changes in HR and BP. Antihistamines may attenuate alcohol skin flushing in alcohol-sensitive individuals with mixed and inconclusive effects on other physiological responses. Current evidence is limited by small sample sizes, inconsistent findings, and a lack of acetaldehyde measurement. These limitations highlight the urgent need for rigorous studies to clarify the health risks of alcohol-antihistamine co-use and to inform harm reduction strategies for vulnerable populations. Understanding these interactions is vital for public health to inform targeted education and interventions.

The persistent effects of exposure to a predator odor stressor on sensitivity to alcohol

ABSTRACT Young adults tend to indulge in risky behaviours. The study utilizes a 10-item AUDIT scale questions and a structured questionnaire on sexual behaviours among school-going young adults to investigate the effect of risky drinking on risky sexual behaviours in the La-Nkwantanang Madina Municipality. A multi-stage sampling technique was utilized. First cluster sampling was used to select 4 schools, consisting of 3 JHS and 1 SHS. Convenience sampling method was used to select university students in the area who were on vacation. The study found that risky drinking was associated with sexual risk behaviours (AOR: 4.23; 95% CI: 2.03–8.83) hence a major predictor of risky sexual behaviours among young adults in the study area. The study found that males were more likely to engage in risky drinking while females were more likely to engage in sexual risk behaviours. The study recommends that alcohol sensitization programmes and sex education be vigorously pursued.

Ethanol inhibits N-methyl-d-aspartate (NMDA) receptors through actions on positions in the membrane-associated (M) domains. Ethanol-insensitive mutant NMDA receptors would be valuable molecular tools for evaluating the roles of NMDA receptors in ethanol actions. However, mutations that decrease ethanol sensitivity also usually alter ion channel gating, which would likely affect glutamatergic synaptic transmission and central nervous system (CNS) function. We selected candidate ethanol-insensitive mutations in the GluN2A and GluN2B subunits with relatively low disruption of ion channel gating: isoleucine substitution at two positions (F636/F637) in M3 of GluN2A and tryptophan substitution at G826 in M4 of GluN2B. Our strategy was to introduce additional mutations in the ligand-binding domain (LBD), if needed, attempting to restore normal receptor kinetics while preserving low alcohol sensitivity. We determined the alcohol sensitivity and gating parameters of the mutant subunits using whole-cell patch-clamp and outside-out patch concentration-jump recording in a cultured cell line. While the majority of GluN2A LBD mutations disrupted receptor function, the GluN2A(E413D/F636I/F637I) mutant subunit had approximately normal glutamate potency while retaining low alcohol sensitivity. LBD mutations were unnecessary in the GluN2B(G826W) subunit because glutamate potency and desensitization were unchanged compared to the wild-type subunit. In concentration-jump experiments, both mutant subunits yielded simulated synaptic currents similar to wild-type currents. The GluN2A(E413D/F636I/F637I) and GluN2B(G826W) mutant subunits exhibit nearly normal physiology and low alcohol sensitivity. These studies also provide evidence that changes in NMDA receptor ethanol sensitivity are not dependent upon changes in ion channel gating.

Animations are effective media that enable researchers to explore, communicate, and gain new insights into complex biological processes.However, the technical complexity and steep learning curve of traditional 3D animation software have hindered their widespread adoption in scientific research.This project addresses these challenges by developing accessible software tools that empower researchers to create their own molecular models and animations.Leveraging the open-source animation software Blender, we are building a suite of tools specifically tailored for molecular animations.These tools will allow users to import Protein Data Bank (PDB) and AlphaFold structural models directly into Blender and build customized molecular representations.Researchers will be able to define conformational states of molecular complexes and generate animated trajectories that transition between these states.Additionally, the tools will support the creation of simplified animations to visualize molecular interactions and movements, offering an intuitive means of depicting complex biological processes.All tools will be implemented as free Blender addons, using Python scripting and Blender's Geometry Nodes procedural system.To enhance accessibility and promote collaboration within the scientific community, we are also developing platforms for archiving, annotating, and sharing animated molecular models.These platforms will enable broader dissemination and use of molecular animations in research and science communication.

Impulsivity and individual differences in alcohol sensitivity (e.g., subjective response to alcohol) have been related to alcohol use behaviors, but scant research has examined how these two constructs are related to each other. Consequently, this pilot study aimed (1) to examine associations between impulsivity domains (impulsive action, impulsive choice, and impulsive personality features) and alcohol sensitivity during alcohol administration in the laboratory; (2) to test daily associations between impulsivity domains and sensitivity to reward during ecological momentary assessment (EMA); and (3) to explore consistency between alcohol sensitivity scores in the lab and EMA. Participants (N = 26; 38.5% male, 61.5% female) were students (graduate and undergraduate) who engaged in recent (past-month) alcohol use and heavy drinking in the past 6 months. Participants completed an in-person alcohol administration session followed by 10 days of EMA. For Aim 1, results indicated that individuals with a greater lack of perseverance reported greater cravings and willingness to drive during the alcohol administration session. Negative and positive urgency were positively associated with liking the alcoholic beverage. For Aim 2, within-person associations revealed that greater than usual lack of premeditation was associated with greater craving while drinking, and greater than usual lack of perseverance was related to less willingness to drive. For Aim 3, subjective effects for liking, craving, and stimulation scores were greater during the EMA portion as compared to the laboratory session. Our findings suggested that individual differences in some impulsive personality features played a role in the motivation to consume alcohol in the laboratory and real world. Future research should replicate these pilot findings and expand on contextual factors that may be driving the present study's associations. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

Genetic influences account for a substantial proportion of individual differences in alcohol use behaviors (AUBs). However, multiple distinct sets of genes are linked to different AUBs via uncertain causal links. Here, we explore whether intermediate neurobiological traits mediate the relationship between polygenic scores (PGSs) and multiple AUBs, with the aim to better understand processes captured by different genetic profiles. We derived four alcohol-related PGSs in participants from Spit for Science, a longitudinal study of college students in the United States (n = 4549). Using linear regression, we tested the relationship between PGSs and 22 potential mediators, including personality, alcohol expectancies, drinking motives, and alcohol sensitivity. Nominally significant effects were carried forward to a multiple mediation model to estimate direct and indirect effects on four measured AUBs (frequency, quantity, alcohol use disorder symptoms [AUDsx], and maximum drinks in 24 h). In univariable regression, PGSs indexing genetic effects on drinks per week (DPW) and problematic alcohol use (PAU) predicted higher levels of impulsivity and drinking motives as well as lower alcohol sensitivity. BeerPref PGSs (indexing a variable pattern of alcohol problems and preference for beer) predicted higher negative urgency and lower alcohol sensitivity. Mediational models indicated direct and indirect effects of DPW PGSs on multiple AUBs via social/enhancement drinking motives and alcohol sensitivity, indirect effects of PAU PGSs on AUDsx, and indirect effects of BeerPref PGS on drinking frequency and AUDsx via the joint effect of mediators including alcohol sensitivity. These findings provide evidence that the genetic influences on AUBs are associated with and partially mediated by intermediate neurobiological and cognitive factors, which may be more amenable to intervention. Greater focus on drinking motives and alcohol sensitivity is warranted in genetic research, as well as attention to the heterogeneous pathways linking genes to alcohol use outcomes.

Lower sensitivity (LS) to acute alcohol promotes hazardous alcohol use, increasing risk for alcohol use disorder (AUD). Compared to peers with high sensitivity (HS), LS individuals exhibit amplified responses to alcohol cues and difficulty exerting inhibitory control (IC) over those cued responses. However, it is unclear whether LS and HS individuals differ in neural or behavioral responses when exerting IC over affectively neutral prepotent responses (i.e., domain-general IC). This fMRI pilot study examined domain-general IC and its neural correlates in young adult LS and HS individuals. Participants (N = 32, M age = 20.3) were recruited based on their Alcohol Sensitivity Questionnaire responses (HS: n = 16; LS: n = 16; 9 females/group) to complete an event-related fMRI IC task in a sober state. Retrospective assessments of alcohol craving, consumption, and problems were taken outside the lab. Although IC performance (accuracy) was numerically lower for the LS group (M[SD] = 0.527[0.125]) compared to the HS group (M[SD] = 0.595[0.124]), no significant difference was detected [t(30) = 1.55, p = 0.132]. Across groups, IC-related activity was observed in bilateral fronto-cortico-striatal circuitry, including dorsal striatum (DS) and dorsal/supragenual anterior cingulate cortex (dACC). Within group HS, IC-related dACC activity was greater among individuals reporting less intense (b-95 CI = [-0.201, -0.041], p = 0.004) and less frequent alcohol craving experiences (b-95 CI = [-0.131, 0.005], p = 0.068), whereas in group LS, IC-related dACC activity was greater among individuals reporting more intense (b-95 CI = [0.009, 0.140], p = 0.028) and more frequent alcohol craving experiences (b-95 CI = [0.022, 0.128], p = 0.007). In sum, while LS and HS individuals demonstrated similar domain-general IC performance and recruited similar neural resources to perform IC, findings suggest that compensatory over-activation of frontocortical nodes of the fronto-cortico-striatal IC circuitry may be related to affective-motivational aspects of AUD symptomatology (craving in daily life) among LS individuals. Based on these preliminary findings, future studies with larger samples are warranted to determine the extent to which domain-general IC performance associated with fronto-cortico-striatal IC circuit activation contributes to the alcohol use pathophysiology, and whether therapeutic interventions (e.g., non-invasive brain stimulation) targeting fronto-cortico-striatal IC circuitry may decrease AUD symptomatology.

Alcohol use is a leading risk factor for preventable death, injury, and disease globally. Low sensitivity to the effects of alcohol is influenced by genes and predicts risk for harmful alcohol use and alcohol use disorder (AUD). Alcohol induces effects partly by modulation of gamma-aminobutyric acid receptors type A (GABAARs). This study investigates the relationship between genetic variation in GABAAR subunit genes and individual alcohol sensitivity among French university students. The study involved 1,409 French university students (34.5% women; mean age 20.3 years). Alcohol sensitivity was measured by the Self-Rating of the Effects of Alcohol Scale (SRE). SRE-scores from initial drinking, regular drinking, and heavy drinking were investigated for correlations with alcohol consumption and for associations with single nucleotide polymorphisms (SNPs) in GABAAR subunit genes (GABRA2, GABRG2, GABRA6). We replicated correlations between low alcohol sensitivity and high alcohol consumption. We further found an association between the minor allele in rs211014 (GABRG2) and higher SRE-scores, linked to dizziness and motor incoordination. Genetic variation in GABRG2 has previously been associated with processes involving motor coordination (alcohol withdrawal, febrile- and epileptic seizures). The results from our study suggest that genetic variation in GABRG2 may influence alcohol sensitivity, which could inform strategies for assessing risk for harmful alcohol use and AUD.

Thin films of ZnO and Al-doped ZnO are deposited on glass wafer substrates using a compressed sprayer system with Zn(CH3COO)2.2H2O and AlCl3 as precursors. The influence of Al doping concentration on the crystal phase and morphology of the samples is investigated by XRD and SEM, respectively. The results show that the films have been crystallized in the form of the wurtzite hexagonal phase of the ZnO lattice, and the addition of Al does not change the ZnO crystal structure. Despite this, SEM images show that added Al significantly affects the particle size of the samples. The particle size decreases and becomes more uniform as the Al concentration increases up to 7%. Further increasing the Al concentration causes the particles to agglomerate into clusters. The resistance measurements show that the sheet resistance of the films decreases in the presence of the Al dopant, providing evidence that Al has been successfully doped into the ZnO crystal lattice. An appropriate amount of Al dopant can improve the alcohol vapor sensitivity of the film. The ZnO film doped with 7% Al exhibits the best alcohol sensitivity.

Background:Genetic influences account for a substantial proportion of individual differences in alcohol use behaviors (AUBs). However, multiple distinct sets of genes are linked to different AUBs, which may explain their dramatic variability in risk factors and manifestations. In this study, we explore whether intermediate neurobiological traits and alcohol-related cognitions mediate the relationship between polygenic scores (PGS) and multiple AUBs, with the aim to better understand processes captured by different genetic profiles.Methods:Using results from prior genome-wide association studies, we derived PGS for 6 AUBs in participants from Spit for Science, a longitudinal study of college students in the U.S. (n=4,549). Self-report measures included personality traits, alcohol expectancies, drinking motivations, and alcohol sensitivity measures as well as drinking frequency, drinking quantity, alcohol use disorder (AUD) symptoms, and maximum drinks in 24 hours. Using linear regression and multiple mediation models, we investigated the direct and indirect effects of PGS on AUBs.Results:In univariable regression results, PGSs indexing broad AUB dimensions such as drinks per week (DPW) and AUD predicted higher levels of sensation-seeking and multiple drinking motives, while BeerPref PGSs (indexing a variable pattern of alcohol problems associated with a preference for beer) predicted higher negative urgency and lower alcohol sensitivity. Mediational models indicated strong direct and indirect effects of DPW PGSs on multiple AUBs via social/enhancement drinking motives and alcohol sensitivity, indirect effects of AUD PGSs on AUD symptoms via coping motives, and indirect effects of BeerPref PGS on all AUBs via the joint effect of mediators including alcohol sensitivity.Conclusions:These findings provide initial evidence that the genetic influences on different AUBs are associated with and partially mediated by intermediate neurobiological and cognitive factors, which may be more amenable to intervention. Greater focus on drinking motives and alcohol sensitivity is warranted in genetic research, as well as attention to the heterogeneous pathways linking genes to alcohol use outcomes.

Alcohol and nicotine interact with the nicotinic acetylcholine receptor system to alter reward-related responses, thereby contributing to the co-use and misuse of these drugs. A missense polymorphism rs16969968 (G>A) in the CHRNA5 gene has shown a strong association with nicotine-related phenotypes. However, less is known about the impact of this variant on alcohol-related phenotypes. We assessed the main and interactive effect of smoking and rs16969968 polymorphism on alcohol consumption using the Alcohol Use Disorders Identification Test (AUDIT), Timeline Follow Back (TLFB), and Lifetime Drinking History (LDH) in 980 healthy adults without alcohol use disorder. We further examined the effect of the rs16969968 polymorphism on acute alcohol consumption using a free-access i.v. alcohol self-administration (IV-ASA) human laboratory paradigm in a subset of 153 nonsmoking participants. Subjective alcohol responses, alcohol sensitivity, and expectancy measures were compared between genotype groups (GG; AA/AG). We observed a significant association of smoking with AUDIT, TLFB, and LDH measures across genotype groups, with smokers showing higher scores compared with nonsmokers. Additionally, we found an association between genotype and TLFB-total drinks in the IV-ASA subset, with the GG group showing higher scores than AA/AG group. Relatedly, the alcohol negative expectancy score was significantly lower in the GG group than the AA/AG group. Our findings underscore the association of smoking with alcohol measures. We found preliminary evidence for the protective effect of the functional CHRNA5 polymorphism on alcohol consumption and its association with increased negative alcohol expectancies, which highlights the substantial heterogeneity in alcohol responses.

Differences in naïve alcohol sensitivity between individuals are a strong predictor of later life alcohol use disorders (AUD). However, the genetic bases for alcohol sensitivity (beyond ethanol metabolism) and pharmacological approaches to modulate alcohol sensitivity remain poorly understood. We used a high-throughput behavioral screen to measure acute behavioral sensitivity to alcohol, a model of intoxication, in a genetically diverse set of over 150 wild strains of the nematode Caenorhabditis elegans. We performed a genome-wide association study to identify loci that underlie natural variation in alcohol sensitivity. We identified five quantitative trait loci (QTL) and further show that variants in the C. elegans ortholog of protein kinase D, dkf-2, likely underlie the chromosome V QTL. We found that resistance to intoxication was conferred by dkf-2 loss-of-function mutations as well as partly by a PKD inhibitor in a dkf-2-dependent manner. Protein kinase D might represent a conserved, druggable target to modify alcohol sensitivity with application towards AUD.

Parenting experiences with caregivers play a key role in neurodevelopment. We recently reported that adolescents reared by a single-mother (SM) display an anxiety-prone phenotype and drink more alcohol, compared to peers derived from a biparental (BP) rearing condition. To investigate if SM and BP offspring infant mice exhibit differential sensitivity to ethanol-induced locomotor activity and differential activity patterns in brain areas related to anxiety response. We also analyzed anxiety response and ethanol-induced anxiolysis in SM and BP adolescents. Mice reared in SM or BP conditions were assessed for (a) ethanol-induced locomotor activity at infancy, (b) central expression of Fos-like proteins (likely represented mostly by FosB, a transcription factor that accumulates after chronic stimuli exposure and serves as a molecular marker of neural plasticity) and cathecolaminergic activity, and (c) anxiety-like behavior and ethanol-induced anxiolysis in adolescence. Infant mice were sensitive to the stimulating effects of 2.0g/kg alcohol, regardless parenting structure. SM mice exhibited, relative to BP mice, a significantly greater number of Fos-like positive cells in the central amygdala and basolateral amygdala nuclei. Ethanol treatment, but not parenting condition, induced greater activation of dopaminergic neurons in ventral tegmental area. SM, but not BP, adolescent mice were sensitive to ethanol-induced anxiolysis. These results highlight the complex relationship between parenting experiences and neurodevelopment. The SM parenting may result in greater neural activation patterns in brain areas associated with anxiety response, potentially contributing to increased basal anxiety and alcohol sensitivity.

Low sensitivity (LS) to alcohol is a risk factor for alcohol use disorder (AUD). Compared to peers with high sensitivity (HS), LS individuals drink more, report more problems, and exhibit potentiated alcohol cue reactivity (ACR). Heightened ACR suggests LS confers AUD risk via incentive sensitization, which is thought to take place in the mesocorticolimbic system. This study examined neural ACR in LS and HS individuals. Young adults (N = 32, Mage=20.3) were recruited based on the Alcohol Sensitivity Questionnaire (HS: n = 16; LS: n = 16; 9 females/group). Participants completed an event-related fMRI ACR task. Group LS had higher ACR in left ventrolateral prefrontal cortex than group HS. In group LS, ACR in left caudomedial orbitofrontal cortex or left putamen was low at low alcohol use levels and high at heavier or more problematic alcohol use levels, whereas the opposite was true in group HS. Alcohol use level also was associated with the level of ACR in left substantia nigra among males in group LS. Taken together, results suggest elevated mesocorticolimbic ACR among LS individuals, especially those using alcohol at hazardous levels. Future studies with larger samples are warranted to determine the neurobiological loci underlying LS-based amplified ACR and AUD risk.