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Increases in harmful drinking among older adults indicate the need for a more thorough understanding of the relationship between later-life alcohol use and brain health. The current study investigated the relationships between alcohol use and progressive grey and white matter changes in older adults using longitudinal data. A total of 530 participants (aged 70 to 90 years; 46.0% male) were included. Brain outcomes assessed over 6 years included total grey and white matter volume, as well as volume of the hippocampus, thalamus, amygdala, corpus callosum, orbitofrontal cortex and insula. White matter integrity was also investigated. Average alcohol use across the study period was the main exposure of interest. Past-year binge drinking and reduction in drinking from pre-baseline were additional exposures of interest. Within the context of low-level average drinking (averaging 11.7 g per day), higher average amount of alcohol consumed was associated with less atrophy in the left (B = 7.50, pFDR = 0.010) and right (B = 5.98, pFDR = 0.004) thalamus. Past-year binge-drinking was associated with poorer white matter integrity (B = -0.013, pFDR = 0.024). Consuming alcohol more heavily in the past was associated with greater atrophy in anterior (B = -12.73, pFDR = 0.048) and posterior (B = -17.88, pFDR = 0.004) callosal volumes over time. Across alcohol exposures and neuroimaging markers, no other relationships were statistically significant. Within the context of low-level drinking, very few relationships between alcohol use and brain macrostructure were identified. Meanwhile, heavier drinking was negatively associated with white matter integrity., (© 2024 The Author(s). Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Adolescence is a brain maturation developmental period during which remodeling and changes in synaptic plasticity and neural connectivity take place in some brain regions. Different mechanism participates in adolescent brain maturation, including autophagy that plays a role in synaptic development and plasticity. Alcohol is a neurotoxic compound and its abuse in adolescence induces neuroinflammation, synaptic and myelin alterations, neural damage and behavioral impairments. Changes in synaptic plasticity and its regulation by mTOR have also been suggested to play a role in the behavioral dysfunction of binge ethanol drinking in adolescence. Therefore, by considering the critical role of mTOR in both autophagy and synaptic plasticity in the developing brain, the present study aims to evaluate whether binge ethanol treatment in adolescence would induce dysfunctions in synaptic plasticity and cognitive functions and if mTOR inhibition with rapamycin is capable of restoring both effects. Using C57BL/6 adolescent female and male mice (PND30) treated with ethanol (3 g/kg) on two consecutive days at 48-hour intervals over 2 weeks, we show that binge ethanol treatment alters the density and morphology of dendritic spines, effects that are associated with learning and memory impairments and changes in the levels of both transcription factor CREB phosphorylation and miRNAs. Rapamycin administration (3 mg/kg) prior to ethanol administration restores ethanol-induced changes in both plasticity and behavior dysfunctions in adolescent mice. These results support the critical role of mTOR/autophagy dysfunctions in the dendritic spines alterations and cognitive alterations induced by binge alcohol in adolescence., (© 2020 International Society of Neuropathology.)

Background: Emerging adulthood is a critical neurodevelopment period in which extreme drinking has a potentially pronounced neurotoxic effect. Therefore, extreme drinking, even a single episode, could be particularly harmful to the developing brain's structure. Relatedly, heavy alcohol use in emerging adults has been associated with structural brain damage, especially in the corpus callosum. However, it is unclear whether and how much a single extreme drinking episode would affect brain morphometry., Methods: For the first time in the literature, the current study prospectively examined the impact of an extreme drinking episode (i.e., twenty-first birthday celebration) on the brain morphometry of emerging adults immediately following their birthday celebration (n = 50) and approximately 5 weeks post-birthday celebration (n = 29)., Results: We found evidence that a single extreme drinking episode was associated with structural changes immediately post-birthday celebration. Specifically, higher twenty-first birthday estimated blood-alcohol concentration was associated with decreased volume of the posterior and central corpus callosum immediately post-birthday celebration. This extreme drinking episode was not associated with further structural changes, or recovery, 5 weeks post-twenty-first birthday celebration., Conclusions: Overall, results suggest that a single episode of heavy drinking in emerging adulthood may be associated with immediate structural changes of the corpus callosum. Thus, emerging adulthood, which is characterized by high rates of extreme drinking, could be a critical period for targeted prevention and intervention., (© 2020 by the Research Society on Alcoholism.)

This review provides the first systematic and quantitative synthesis of the literature examining the relationship between binge drinking, cognition, brain structure and function in youth aged 10 to 24 years. PubMed, EMBASE, Medline, PsychINFO and ProQuest were searched for neuroimaging, neurophysiological, and neuropsychological studies. A total of 58 studies (21 neuroimaging, 16 neurophysiological, 21 neuropsychological) met the eligibility criteria and were included in the review. Overall, abnormal or delayed development of key frontal executive-control regions may predispose youth to binge drink. These abnormalities appear to be further exacerbated by the uptake of binge drinking, in addition to alcohol-related neural aberrations in reward-seeking and incentive salience regions, indexed by cognitive deficits and maladaptive alcohol associations. A meta-analysis of neuropsychological correlates identified that binge drinking in youth was associated with a small overall neurocognitive deficit (g = -0.26) and specific deficits in decision-making (g = -1.70), and inhibition (g = -0.39). Using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) Evidence Profile, the certainty in outcomes ranged from very low to low. Future prospective longitudinal studies should address concomitant factors, exposure thresholds, and age-related vulnerabilities of binge drinking, as well as the degree of recovery following discontinuation of use.

Aims: Microarray analysis of hippocampal tissue from chronic binge alcohol (CBA)-administered, simian immunodeficiency virus (SIV)-infected male macaques identified altered immune response and neurogenesis as potential mechanisms underlying cognitive deficits in macaques. This study investigated the differential brain region associations between markers of neuroinflammation and growth factor signaling with microtubule-associated protein 2 (MAP2) expression., Methods: Adult male rhesus macaques were administered CBA (13-14 g EtOH/kg/week, n = 8) or sucrose (SUC, n = 7) beginning 3 months prior to SIV infection and continued until animals reached end-stage disease criteria (3-24 months post infection). Expression of inflammatory cytokines, growth factors, and viral loads were determined in the prefrontal cortex (PFC), caudate (CD), and hippocampus (HP). Brain-derived neurotropic factor (BDNF) expression and phosphorylation of intracellular kinases downstream of BDNF were investigated in the PFC., Results: Our results show reduced MAP2 expression in the PFC of longer-surviving, CBA/SIV macaques. BDNF expression was most closely associated with MAP2 expression in the PFC. In the caudate, significant positive associations were observed between MAP2 and BDNF, time to end-stage and set-point viral load and significant negative associations for CBA. In the hippocampus, positive associations were observed between MAP2 and inflammatory cytokines, and negative associations for brain viral load and CBA., Conclusions: CBA differentially affects growth factor and inflammatory cytokine expression and viral load across brain regions. In the PFC, suppression of growth factor signaling may be an important neuropathological mechanism, while inflammatory processes may play a more important role in the CD and HP., (© The Author(s) 2019. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

Alcohol abuse causes brain damage and cognitive dysfunction. However, the underlying mechanisms remain elusive. Endoplasmic reticulum (ER) acts as machinery to ensure the proper folding of newly synthesized proteins. The perturbation of ER, i.e., ER stress, plays a pivotal role in some neurological disorders. Mammalian target of rapamycin (mTOR), a serine/threonine kinase, is involved in the regulation of ER stress. The current study sought to determine whether binge ethanol exposure induces ER stress in adult mouse brain and the role mTOR signaling during this process. Adult C57BL6 mice received binge ethanol exposure by daily gavage (5 g/kg, 25% ethanol w/v) for 1, 5 or 10 days. Binge ethanol exposure caused neurodegeneration and neuroinflammation after 5 days of exposure, and a concomitant increase of ER stress and inhibition of mTOR. However, ethanol exposure did not significantly alter spatial learning and memory, and spontaneous locomotor activity. Ethanol treatment induced ER stress and the death of cultured neuronal cells. Cotreatment with an ER stress inhibitor, sodium 4-phenylbutyrate (4-PBA) significantly diminished ethanol-induced ER stress and neuronal apoptosis, suggesting that ER stress contributes to ethanol-induced neurodegeneration. Furthermore, the blockage of mTOR activity by rapamycin increased ER stress in cultured neuronal cells; whereas the activation or inhibition of ER stress by tunicamycin or 4-PBA respectively had little effects on mTOR signaling. These results suggested that mTOR signaling is upstream of ER stress and may thereby mediate ethanol-induced ER stress., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Adolescence is a critical stage of brain maturation in which important plastic and dynamic processes take place in different brain regions, leading to development of the adult brain. Ethanol drinking in adolescence disrupts brain plasticity and causes structural and functional changes in immature brain areas (prefrontal cortex, limbic system) that result in cognitive and behavioral deficits. These changes, along with secretion of sexual and stress-related hormones in adolescence, may impact self-control, decision making, and risk-taking behaviors that contribute to anxiety and initiation of alcohol consumption. New data support the participation of the neuroimmune system in the effects of ethanol on the developing and adult brain. This article reviews the potential pathological bases that underlie the effects of alcohol on the adolescent brain, such as the contribution of genetic background, the perturbation of epigenetic programming, and the influence of the neuroimmune response. Special emphasis is given to the actions of ethanol in the innate immune receptor toll-like receptor 4 (TLR4), since recent studies have demonstrated that by activating the inflammatory TLR4/NFκB signaling response in glial cells, binge drinking of ethanol triggers the release of cytokines/chemokines and free radicals, which exacerbate the immune response that causes neuroinflammation/neural damage as well as short- and long-term neurophysiological, cognitive, and behavioral dysfunction. Finally, potential treatments that target the neuroimmune response to treat the neuropathological and behavioral consequences of adolescent alcohol abuse are discussed., (© 2017 Wiley Periodicals, Inc.)

In the young population, binge drinking is a pattern of problematic alcohol consumption, characterized by a short period of heavy drinking followed by abstinence which is frequently repeated over time. This drinking pattern is associated with mental problems, use of other drugs, and an increased risk of excessive alcohol intake during adulthood. However, little is known about the effects of binge drinking on brain function in adolescents and its neurobiological impact during the adulthood. In the present study, we evaluated the effects of alcohol on hippocampal memory, synaptic plasticity, and mitochondrial function in adolescent rats after a binge drinking episode in vivo. These effects were analyzed at 1, 3, or 7 weeks post alcohol exposure. Our results showed that binge-like ethanol pre-treated (BEP) rats exhibited early alterations in learning and memory tests accompanied by an impairment of synaptic plasticity that was total and partially compensated, respectively. These changes could be attributed to a rapid increase in oxidative damage and a late inflammatory response induced by post ethanol exposure. Additionally, BEP alters the regulation of mitochondrial dynamics and modifies the expression of mitochondrial permeability transition pore (mPTP) components, such as cyclophilin D (Cyp-D) and the voltage-dependent anion channel (VDAC). These mitochondrial structural changes result in the impairment of mitochondrial bioenergetics, decreasing ATP production progressively until adulthood. These results strongly suggest that teenage alcohol binge drinking impairs the function of the adult hippocampus including memory and synaptic plasticity as a consequence of the mitochondrial damage induced by alcohol and that the recovery of hippocampal function could implicate the activation of alternative pathways that fail to reestablish mitochondrial function.

Binge drinking is a pattern of alcohol drinking that raises a person's blood alcohol concentration to at least .08%, which amounts to consuming five alcoholic drinks for men and four alcoholic drinks for women in about 2 hours. It is the most common form of alcohol misuse in adolescents and young adults. Heavy drinking includes the same criterion as binge drinking, but with higher frequency (i.e., 5 or more days in the past 30 days). Although binge drinking or heavy drinking alone is insufficient to meet the criteria for an alcohol use disorder (AUD) diagnosis, there are neurobiological changes, as well as an increased risk of developing an AUD later in life, associated with this form of alcohol misuse. This review describes the recent neuroimaging findings in binge drinking and heavy-drinking adolescents and young adults, a developmental period during which significant neuromaturation occurs.

The assessment of binge ethanol-induced neuronal activation, using c-Fos immunoreactivity (IR) as a marker of neuronal activity, is typically accomplished via forced ethanol exposure, such as intraperitoneal injection or gavage. Neuronal activity using a voluntary binge-like drinking model, such as "drinking-in-the-dark" (DID), has not been thoroughly explored. Additionally, studies assessing ethanol-elicited neuronal activation may or may not involve stereotaxic surgery, which could impact c-Fos IR. The experiments detailed herein aimed to assess the effects of voluntary binge-like ethanol consumption on c-Fos IR in brain regions implicated in ethanol intake in animals with and without surgery experience. Age-matched male C57BL/6J mice underwent either stereotaxic surgery (Study 1) or no surgery (Study 2). Then, mice experienced one 4-day DID cycle, tail blood samples were collected immediately after test conclusion on day 4, and mice were subsequently sacrificed. In each study, mice that drink ethanol were sorted into those that achieved binge-equivalent blood ethanol concentrations (BECs ≥ 80 mg/dl) versus those that did not. Relative to water-consuming controls, mice with BECs ≥ 80 mg/dl showed significantly elevated c-Fos IR in several brain regions implicated in neurobiological responses to ethanol. In general, the brain regions exhibiting binge-induced c-Fos IR were the same between studies, though differences were noted, highlighting the need for caution when interpreting ethanol-induced c-Fos IR when subjects have a prior history of surgery. Altogether, these results provide insight into the brain regions that modulate binge-like ethanol intake stemming from DID procedures among animals with and without surgery experience., (Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.)

The current study used diffusion tensor imaging to examine patterns/degree of brain connectivity in 12 college-aged binge drinking (BD) and 12 moderate drinking individuals. Voxel-level and region-of-interest analyses revealed increased connectivity of the BD brain in the right corona radiata, right external capsule, and both the right and left cingulum. Also, fractional anisotropy and axial diffusivity values of these regions correlated with a number of drinking behaviors of the BD as well as both groups combined. It is hypothesized that increased connectivity in the BD may produce difficulties with regulatory control, contributing to their propensity to binge.

Background: Recent studies have implicated microglia-the resident immune cells of the brain-in the pathophysiology of alcoholism. Indeed, post-mortem alcoholic brains show increased microglial markers and increased immune gene expression; however, the effects of ethanol on microglial functioning and how this impacts the brain remain unclear. In this present study, we investigate the effects of acute binge ethanol on microglia and how microglial depletion changes the brain neuroimmune response to acute binge ethanol withdrawal., Methods: C57BL/6J mice were treated intragastrically with acute binge ethanol for time course and dose-response studies. Cultured mouse BV2 microglia-like cells were treated with ethanol in vitro for time course studies. Mice were also administered the colony stimulating factor 1 receptor (CSF1R) inhibitor PLX5622 to deplete microglia from the brain. These mice were subsequently treated with acute binge ethanol and sacrificed during withdrawal. Brain and BV2 mRNA were isolated and assessed using RT-PCR to examine expression of microglial and neuroimmune genes., Results: Acute binge ethanol biphasically changed microglial (e.g., Iba1, CD68) gene expression, with initial decreases during intoxication and subsequent increases during withdrawal. Acute ethanol withdrawal dose dependently increased neuroimmune gene (e.g., TNFα, Ccl2, IL-1ra, IL-4) expression beginning at high doses. BV2 cells showed biphasic changes in pro-inflammatory (e.g., TNFα, Ccl2) gene expression following ethanol treatment in vitro. Administration of PLX5622 depleted microglia from the brains of mice. Although some neuroimmune genes were reduced by microglial depletion, many others were unchanged. Microglial depletion blunted pro-inflammatory (e.g., TNFα, Ccl2) gene expression and enhanced anti-inflammatory (e.g., IL-1ra, IL-4) gene expression during acute binge ethanol withdrawal., Conclusions: These studies find acute binge ethanol withdrawal increases microglial and neuroimmune gene expression. Ethanol exposure also increases microglial pro-inflammatory gene expression in vitro. Furthermore, microglial depletion decreases expression of microglia-specific genes but has little effect on expression of many other neuroimmune signaling genes. Microglial depletion blunted the acute binge ethanol withdrawal induction of pro-inflammatory genes and enhanced induction of anti-inflammatory genes. These findings indicate microglia impact the brain response to acute binge ethanol withdrawal.

Fetal alcohol spectrum disorder (FASD) is a leading potentially preventable birth defect. Poor nutrition may contribute to adverse developmental outcomes of prenatal alcohol exposure, and supplementation of essential micronutrients such as choline has shown benefit in rodent models. The sheep model of first-trimester binge alcohol exposure was used in this study to model the dose of maternal choline supplementation used in an ongoing prospective clinical trial involving pregnancies at risk for FASD. Primary outcome measures including volumetrics of the whole brain, cerebellum, and pituitary derived from magnetic resonance imaging (MRI) in 6-month-old lambs, testing the hypothesis that alcohol-exposed lambs would have brain volume reductions that would be ameliorated by maternal choline supplementation. Pregnant sheep were randomly assigned to one of five groups - heavy binge alcohol (HBA; 2.5 g/kg/treatment ethanol), heavy binge alcohol plus choline supplementation (HBC; 2.5 g/kg/treatment ethanol and 10 mg/kg/day choline), saline control (SC), saline control plus choline supplementation (SCC; 10 mg/kg/day choline), and normal control (NC). Ewes were given intravenous alcohol (HBA, HBC; mean peak BACs of ∼280 mg/dL) or saline (SC, SCC) on three consecutive days per week from gestation day (GD) 4-41; choline was administered on GD 4-148. MRI scans of lamb brains were performed postnatally on day 182. Lambs from both alcohol groups (with or without choline) showed significant reductions in total brain volume; cerebellar and pituitary volumes were not significantly affected. This is the first report of MRI-derived volumetric brain reductions in a sheep model of FASD following binge-like alcohol exposure during the first trimester. These results also indicate that maternal choline supplementation comparable to doses in human studies fails to prevent brain volume reductions typically induced by first-trimester binge alcohol exposure. Future analyses will assess behavioral outcomes along with regional brain and neurohistological measures., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Young adult university students frequently binge on alcohol and have high stress levels. Based on findings in rodents, we predicted that heavy current alcohol use and elevated stress and depression scores would be associated with deficits on high interference memory tasks, while early onset, prolonged binge patterns would lead to broader cognitive deficits on tests of associative encoding and executive functions. We developed the Concentration Memory Task, a novel computerized version of the Concentration card game with a high degree of interference. We found that young adults with elevated stress, depression, and alcohol consumption scores were impaired in the Concentration Memory Task. We also analyzed data from a previous study, and found that higher alcohol consumption scores were associated with impaired performance on another high interference memory task, based on Kirwan and Stark's Mnemonic Similarity Test. On the other hand, adolescent onset of binge drinking predicted poorer performance on broader range of memory tests, including a more systematic test of spatial recognition memory, and an associative learning task. Our results are broadly consistent with findings in rodents that acute alcohol and stress exposure suppress neurogenesis in the adult hippocampus, which in turn impairs performance in high interference memory tasks, while adolescent onset binge drinking causes more extensive brain damage and cognitive deficits., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Binge consumption of alcohol is a major societal problem associated with important cognitive, physiological and neurotoxic consequences. Converging evidence highlights the need to assess binge drinking (BD) and its effects on the developing brain while taking into account gender differences. Here, we compared the brain volumetric differences between genders in college-aged binge drinkers and healthy volunteers., Method: T1-weighted magnetic resonance imaging (MRI) images of 30 binge drinkers (18 males) and 46 matched healthy volunteers (23 males) were examined using voxel-based morphometry. The anatomical scans were covaried with Alcohol Use Disorders Identification Test (AUDIT) scores. Whole brain voxel-wise group comparisons were performed using a cluster extent threshold correction., Results: Several large clusters qualified with group-by-gender interactions were observed in prefrontal, striatal and medial temporal areas, whereby BD females had more volume than non-BD females, while males showed the inverse pattern of decreased volume in BD males and increased volume in non-BD males. AUDIT scores negatively correlated with volume in the right superior frontal cortex and precentral gyrus., Conclusions: These findings dovetail with previous studies reporting that a state effect of BD in college-aged drinkers and the severity of alcohol use are associated with volumetric alterations in the cortical and subcortical areas of the brain. Our study indicates that these widespread volumetric changes vary differentially by gender, suggesting either sexual dimorphic endophenotypic risk factors, or differential neurotoxic sensitivities for males and females.

Developmental changes in structure and functioning are thought to make the adolescent brain particularly sensitive to the negative effects of alcohol. Although alcohol use disorders are relatively rare in adolescence, the initiation of alcohol use, including problematic use, becomes increasingly prevalent during this period. The present study examined associations between normative drinking (alcohol initiation, binge drinking, intoxication) and brain morphometry in a sample of 96 adolescent monozygotic twins. A priori regions of interest included 11 subcortical and 20 cortical structures implicated in the existing empirical literature as associated with normative alcohol use in adolescence. In addition, co-twin control analyses were used to disentangle risk for alcohol use from consequences of alcohol exposure on the developing brain. Results indicated significant associations reflecting preexisting vulnerability toward problematic alcohol use, including reduced volume of the amygdala, increased volume of the cerebellum, and reduced cortical volume and thickness in several frontal and temporal regions, including the superior and middle frontal gyri, pars triangularis, and middle and inferior temporal gyri. Results also indicated some associations consistent with a neurotoxic effect of alcohol exposure, including reduced volume of the ventral diencephalon and the middle temporal gyrus., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Binge drinking is common during adolescence and can lead to the development of psychiatric disorders, including alcoholism in adulthood. Here, the role and persistent effects of histone modifications during adolescent intermittent ethanol (AIE) exposure in the development of anxiety and alcoholism in adulthood were investigated. Rats received intermittent ethanol exposure during post-natal days 28-41, and anxiety-like behaviors were measured after 1 and 24 h of the last AIE. The effects of AIE on anxiety-like and alcohol-drinking behaviors in adulthood were measured with or without treatment with the histone deacetylase (HDAC) inhibitor, trichostatin A (TSA). Amygdaloid brain regions were collected to measure HDAC activity, global and gene-specific histone H3 acetylation, expression of brain-derived neurotrophic factor (BDNF) and activity-regulated cytoskeleton-associated (Arc) protein and dendritic spine density (DSD). Adolescent rats displayed anxiety-like behaviors after 24 h, but not 1 h, of last AIE with a concomitant increase in nuclear and cytosolic amygdaloid HDAC activity and HDAC2 and HDAC4 levels leading to deficits in histone (H3-K9) acetylation in the central (CeA) and medial (MeA), but not in basolateral nucleus of amygdala (BLA). Interestingly, some of AIE-induced epigenetic changes such as, increased nuclear HDAC activity, HDAC2 expression, and decreased global histone acetylation persisted in adulthood. In addition, AIE decreased BDNF exons I and IV and Arc promoter specific histone H3 acetylation that was associated with decreased BDNF, Arc expression and DSD in the CeA and MeA during adulthood. AIE also induced anxiety-like behaviors and enhanced ethanol intake in adulthood, which was attenuated by TSA treatment via normalization of deficits in histone H3 acetylation of BDNF and Arc genes. These novel results indicate that AIE induces long-lasting effects on histone modifications and deficits in synaptic events in the amygdala, which are associated with anxiety-like and alcohol drinking behaviors in adulthood., (Published by Elsevier Inc.)

Gestational exposure to alcohol can result in long-lasting behavioral deficiencies generally described as fetal alcohol spectrum disorder (FASD). FASD-modeled rodent studies of acute ethanol exposure typically select one developmental window to simulate a specific context equivalent of human embryogenesis, and study consequences of ethanol exposure within that particular developmental epoch. Exposure timing is likely a large determinant in the neurobehavioral consequence of early ethanol exposure, as each brain region is variably susceptible to ethanol cytotoxicity and has unique sensitive periods in their development. We made a parallel comparison of the long-term effects of single-day binge ethanol at either embryonic day 8 (E8) or postnatal day 7 (P7) in male and female mice, and here demonstrate the differential long-term impacts on neuroanatomy, behavior and in vivo electrophysiology of two systems with very different developmental trajectories. The significant long-term differences in odor-evoked activity, local circuit inhibition, and spontaneous coherence between brain regions in the olfacto-hippocampal pathway that were found as a result of developmental ethanol exposure, varied based on insult timing. Long-term effects on cell proliferation and interneuron cell density were also found to vary by insult timing as well as by region. Finally, spatial memory performance and object exploration were affected in P7-exposed mice, but not E8-exposed mice. Our physiology and behavioral results are conceptually coherent with the neuroanatomical data attained from these same mice. Our results recognize both variable and shared effects of ethanol exposure timing on long-term circuit function and their supported behavior., (Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.)

Background: Abnormal decision making under risk is associated with a number of psychiatric disorders. Here, we focus on binge drinkers (BD), characterized by repeated episodes of heavy alcohol intoxication. Previous studies suggest a decreased sensitivity to aversive conditioning in BD. Here, we asked whether BD might be characterized by enhanced risk seeking related to decreased sensitivity to the anticipation of negative outcomes., Methods: Using an anticipatory risk-taking task (40 BD and 70 healthy volunteers) and an adapted version of this task for functional magnetic resonance imaging (21 BD and 21 healthy volunteers), we assessed sensitivity to reward and loss across risk probabilities., Results: In the behavioral task, BD showed a higher number of risky choices in high-risk losses. In the neuroimaging task, the high-risk attitude in the loss condition was associated with greater activity in dorsolateral prefrontal, lateral orbitofrontal, and superior parietal cortices in BD. Explicit exposure of BD to the probability and magnitude of loss, via introduction of feedback, resulted in a subsequent decrease in risky choices. This change in risk attitude in BD was associated with greater activity in inferior frontal gyrus, which also correlated with the percentage of decrease in risky choices after feedback presentation, suggesting a possible role for cognitive control toward risk-seeking attitudes., Conclusions: Our findings suggest that a decrease in sensitivity to the anticipation of high-risk negative outcomes might underlie BD behavior. Presentation of explicit feedback of probability and loss in BD can potentially modify risk-taking attitudes, which have important public health implications and suggest possible therapeutic targets., (© 2013 Society of Biological Psychiatry Published by Society of Biological Psychiatry All rights reserved.)

Rationale: Ventricular enlargement is a robust phenotype of the chronically dependent alcoholic human brain, yet the mechanism of ventriculomegaly is unestablished. Heterogeneous stock Wistar rats administered binge EtOH (3 g/kg intragastrically every 8 h for 4 days to average blood alcohol levels (BALs) of 250 mg/dL) demonstrate profound but reversible ventricular enlargement and changes in brain metabolites (e.g., N-acetylaspartate (NAA) and choline-containing compounds (Cho))., Objectives: Here, alcohol-preferring (P) and alcohol-nonpreferring (NP) rats systematically bred from heterogeneous stock Wistar rats for differential alcohol drinking behavior were compared with Wistar rats to determine whether genetic divergence and consequent morphological and neurochemical variation affect the brain's response to binge EtOH treatment., Methods: The three rat lines were dosed equivalently and approached similar BALs. Magnetic resonance imaging and spectroscopy evaluated the effects of binge EtOH on brain., Results: As observed in Wistar rats, P and NP rats showed decreases in NAA. Neither P nor NP rats, however, responded to EtOH intoxication with ventricular expansion or increases in Cho levels as previously noted in Wistar rats. Increases in ventricular volume correlated with increases in Cho in Wistar rats., Conclusions: The latter finding suggests that ventricular volume expansion is related to adaptive changes in brain cell membranes in response to binge EtOH. That P and NP rats responded differently to EtOH argues for intrinsic differences in their brain cell membrane composition. Further, differential metabolite responses to EtOH administration by rat strain implicate selective genetic variation as underlying heterogeneous effects of chronic alcoholism in the human condition.

Classically, disorders associated with 'alcohol-related brain damage' (ARBD) occur as a result of chronic excessive alcohol misuse and confer significant physical and psychological disability to the individual as well as to the community. These phenotypes are often difficult to detect at early stages and therefore early intervention and treatment is limited. It remains unresolved as to whether there are neurobiological markers of the early stages of such brain damage in young 'at-risk' drinkers, who probably experience 'alcohol-induced brain impairment' prior to the onset of ARBD, per se. This review focuses on neurobiological (in particular, neuropsychological and neuroimaging) markers that are associated with alcohol misuse in young people (13-24 years of age). The findings from this review suggest that a clearer understanding of alcohol misuse (particularly with regards to binge drinking) is needed. Despite this, neurocognitive profile along with supporting neuroimaging evidence appears to be particularly important in the early detection of brain changes that result from excessive alcohol use. In young alcohol misusers, these preventable and potentially reversible deficits may be progressive but if left unresolved such deficits eventually become major contributors to poor outcome (long term) and hamper adherence to treatment. We address five key themes in this review: (i) there are specific drinking patterns in young people; (ii) youth represents a critical period in brain development that is particularly vulnerable to alcohol misuse; (iii) the extent to which there are pre-existing versus alcohol-induced neurobiological changes remains unclear; (iv) vulnerability markers may be mediated by mental health and substance use comorbidities; and (v) cognitive remediation would be a likely candidate for early prevention and treatment as it could help to develop efficient meta-cognitive skills to prevent relapse in young drinkers., (Copyright © 2012 Elsevier Ltd. All rights reserved.)