Regulation Of Alcohol Consumption Research Articles

Campus Officials’ Perceptions of Alcohol Policies for College Sporting Events

Campus Officials’ Perceptions of Alcohol Policies for College Sporting Events

Effects of social housing on alcohol intake in mice depend on the non-social environment.

Excessive alcohol consumption leads to serious health problems. Mechanisms regulating the consumption of alcohol are insufficiently understood. Previous preclinical studies suggested that non-social environmental and social environmental complexities can regulate alcohol consumption in opposite directions. However, previous studies did not include all conditions and/or did not include female rodents. Therefore, in this study, we examined the effects of social versus single housing in standard versus non-standard housing conditions in male and female mice. Adult C57BL/6 J mice were housed in either standard shoebox cages or in automated Herdsman 2 (HM2) cages and exposed to a two-bottle choice procedure with 3% or 6% ethanol versus water for 5 days. The HM2 cages use radiotracking devices to measure the fluid consumption of individual mice in an undisturbed and automated manner. In both housing conditions, mice were housed either at one or at four per cage. In standard cages, group housing of animals decreased alcohol consumption and water consumption. In HM2 cages, group housing significantly increased ethanol preference and decreased water intake. There were no significant differences in these effects between male and female animals. These observations were similar for 3 and 6% ethanol solutions but were more pronounced for the latter. The effects of social environment on ethanol preference in HM2 cages were accompanied by an increase in the number of approaches to the ethanol solution and a decrease in the number of approaches to water. The differences in ethanol intake could not be explained by differences in locomotor or exploratory activity as socially housed mice showed fewer non-consummatory visits to the ethanol solutions than single-housed animals. In addition, we observed that significant changes in behaviors measuring the approach to the fluid were not always accompanied by significant changes in fluid consumption, and vice versa, suggesting that it is important to assess both measures of motivation to consume alcohol. Our results indicate that the direction of the effects of social environment on alcohol intake in mice depends on the non-social housing environment. Understanding mechanisms by which social and non-social housing conditions modulate alcohol intake could suggest approaches to counteract environmental factors enhancing hazardous alcohol consumption.

Alcohol-related liver disease: A global perspective

Alcohol-associated liver disease (ALD) represents one of the deadliest yet preventable consequences of excessive alcohol use. It represents 5.1 % of the global burden of disease, mainly involving the productive-age population (15-44 years) and leading to an increased mortality risk from traffic road injuries, suicide, violence, cardiovascular disease, neoplasms, and liver disease, among others, accounting for 5.3 % of global deaths. Daily alcohol consumption, binge drinking (BD), and heavy episodic drinking (HED) are the patterns associated with a higher risk of developing ALD. The escalating global burden of ALD, even exceeding what was predicted, is the result of a complex interaction between the lack of public policies that regulate alcohol consumption, low awareness of the scope of the disease, late referral to specialists, underuse of available medications, insufficient funds allocated to ALD research, and non-predictable events such as the COVID-19 pandemic, where increases of up to 477 % in online alcohol sales were registered in the United States. Early diagnosis, referral, and treatment are pivotal to achieving the therapeutic goal in patients with alcohol use disorder (AUD) and ALD, where complete alcohol abstinence and prevention of alcohol relapse are expected to enhance overall survival. This can be achieved through a combination of cognitive behavioral, motivational enhancement and pharmacological therapy. Furthermore, the appropriate use of available pharmacological therapy and implementation of public policies that comprehensively address this disease will make a real difference.

Distinct roles of the left and right prelimbic cortices in the modulation of ethanol consumption in male mice under acute and chronic social defeat stress.

Chronic stress exposure disrupts the medial prefrontal cortex's (mPFC) ability to regulate impulses, leading to the loss of control over alcohol drinking in rodents, emphasizing the critical role of this forebrain area in regulating alcohol consumption. Moreover, chronic stress exposure causes lateralization of mPFC functions with volumetric and functional changes, resulting in hyperactivity in the right hemisphere and functional decrease in the left. This study investigated the inhibitory role of the left prelimbic cortex (LPrL) on ethanol consumption induced by chronic social defeat stress (SDS) in male mice and to examine if inactivation of the LPrL causes disinhibition of the right mPFC, leading to an increase in ethanol consumption. We also investigated the role of lateralization and neurochemical alterations in the mPFC related to ethanol consumption induced by chronic SDS. To this end, we examined the activation patterns of ΔFosB, VGLUT2, and GAD67 in the left and right mPFC. Temporarily blocking the LPrL or right PrL (RPrL) cortices during acute SDS did not affect male mice's voluntary ethanol consumption in male mice. When each cortex was blocked in mice previously exposed to chronic SDS, ethanol consumption also remained unaffected. However, male mice with LPrL lesions during chronic SDS showed an increase in voluntary ethanol consumption, which was associated with enhanced ΔFosB/VGLUT2-positive neurons within the RPrL cortex. The results suggest that the LPrL may play a role in inhibiting ethanol consumption induced by chronic SDS, while the RPrL may be involved in the disinhibition of ethanol consumption.

АНАЛИЗ И СОВЕРШЕНСТВОВАНИЕ АКЦИЗНОЙ ПОЛИТИКИ РОССИЙСКОЙ ФЕДЕРАЦИИ В ОТНОШЕНИИ АЛКОГОЛЬНОЙ ПРОДУКЦИИ

The article analyses the measures of the state anti-alcohol policy of modern Russia in the field of taxation and assessment of their impact on the receipt of excise taxes in the budget of the Russian Federation and the level of consumption of alcoholic beverages by the adult population of the country. Particular attention is paid to the study of the excise policy of the Russian Federation in relation to alcoholic beverages. Excise taxation is one of the effective instruments of state regulation of the production and consumption of alcoholic beverages. The purpose of the study is, based on the analysis, to develop recommendations for changing excise tax rates on various types of alcoholic products to enhance the fiscal potential of excise taxes and regulate alcohol consumption by the country's population. The study was carried out using methods of systematic comparative analysis of domestic and foreign literature and statistical data, as well as generalization and synthesis. It highlights the structure and dynamics of excise tax revenues to the budget of the Russian Federation by type of alcoholic beverages. It also considers restrictive measures relating to the production, sale and consumption of alcoholic beverages in Russia, as well as options for tax support for domestic producers of low-alcohol drinks. A study of the dynamics of the volume and structure of consumption of alcoholic beverages by the population showed the high effectiveness of government regulatory measures, including excise taxation instruments. However, despite the identified reduction, the level of alcohol consumption by the population of the Russian Federation remains high, which raises the need to improve excise policy in the field of taxation of alcoholic products. The increase in excise tax rates on strong alcohol and a change in the method of levying excise tax on beer proposed by the authors will ensure annual additional excise tax revenues to the budget, will lead to a reduction in the consumption of alcoholic beverages and a shift in consumer preferences towards low-alcohol drinks that cause less harm to human health.

Chemogenetic Perturbation of the Posterior But Not Anterior Cerebellum Reduces Voluntary Ethanol Consumption.

The cerebellum communicates with brain areas critically involved in control of goal-directed behaviors including the prefrontal and orbitofrontal cortices and midbrain and basal ganglia structures. In particular, the posterior cerebellum is important for cognitive flexibility and has been implicated in alcohol and drug-related memory. We hypothesized that the cerebellum, through its multiple connections to reward-related brain circuitry, regulates alcohol consumption. To test this, we expressed inhibitory designer receptors exclusively activated by designer drugs (DREADDs) in molecular layer interneurons (MLIs) in anterior (IV-V) or posterior (VI-VIII) cerebellar lobules of male and female mice and activated them during alcohol drinking sessions. In a home-cage drinking paradigm, alcohol consumption was significantly decreased by clozapine-N-oxide (CNO) or deschloroclozapine (DCZ) administration in male mice expressing DREADDs in posterior but not anterior lobules. CNO/DCZ injections did not affect drinking in DREADD expressing female mice or in male mice expressing the control vector. Activation of DREADDs expressed in anterior or posterior lobules had no effect on sucrose or quinine consumption in male or female mice. During operant self-administration sessions, DCZ decreased the number of licks and bouts in male but not female mice expressing DREADDs in posterior lobules with no effect in control vector mice. Performance on an accelerated rotarod was unaffected by chemogenetic manipulation while distance traveled in the open field was decreased by DREADD activation in anterior but not posterior lobules. These results indicate that neuronal activity within the posterior cerebellar cortex plays an important role in the control of alcohol consumption in male mice.

N-oleoyl glycine and N-oleoyl alanine attenuate alcohol self-administration and preference in mice

The endocannabinoid system (ECS) plays a key modulatory role during synaptic plasticity and homeostatic processes in the brain and has an important role in the neurobiological processes underlying drug addiction. We have previously shown that an elevated ECS response to psychostimulant (cocaine) is involved in regulating the development and expression of cocaine-conditioned reward and sensitization. We therefore hypothesized that drug-induced elevation in endocannabinoids (eCBs) and/or eCB-like molecules (eCB-Ls) may represent a protective mechanism against drug insult, and boosting their levels exogenously may strengthen their neuroprotective effects. Here, we determine the involvement of ECS in alcohol addiction. We first measured the eCBs and eCB-Ls levels in different brain reward system regions following chronic alcohol self-administration using LC–MS. We have found that following chronic intermittent alcohol consumption, N-oleoyl glycine (OlGly) levels were significantly elevated in the prefrontal cortex (PFC), and N-oleoyl alanine (OlAla) was significantly elevated in the PFC, nucleus accumbens (NAc) and ventral tegmental area (VTA) in a region-specific manner. We next tested whether exogenous administration of OlGly or OlAla would attenuate alcohol consumption and preference. We found that systemic administration of OlGly or OlAla (60 mg/kg, intraperitoneal) during intermittent alcohol consumption significantly reduced alcohol intake and preference without affecting the hedonic state. These findings suggest that the ECS negatively regulates alcohol consumption and boosting selective eCBs exogenously has beneficial effects against alcohol consumption and potentially in preventing relapse.

Políticas públicas como factor protector del consumo de alcohol en universitarios mexicanos

IntroductionIn environments where public policies regulating alcohol consumption are stricter, alcohol consumption decreases, by virtue of reduced availability, marketing, and price regulation of alcoholic beverages. ObjectiveTo determine the relationship and effect of the perception of policies to reduce alcohol-related problems with alcohol consumption and the four prevalence of alcohol consumption in young Mexican university students. MethodologyA descriptive, correlational and predictive study with a sample of 367 students from a public university in the state of Tabasco, Mexico, selected by stratified random probability sampling. A Personal Data and Prevalence of Alcohol Consumption Questionnaire, the Scale of Support for Public Policies to Reduce Problems Associated with Alcohol and the Alcohol Use Disorder Identification Test (AUDIT) were used. The study adhered to the provisions of the Regulations of the General Health Law on Research. ResultsThe general index of perception of public policies was negatively and significantly related (rs=−.34, P<.001) with alcohol consumption and with the three types of consumption, low risk, dependent and harmful. Perception of harm reduction public policy (B=−.356, P<.001) was identified as a predictor of alcohol consumption in college youth. The general index of perception of public policies has a protective effect on current and instantaneous prevalence (OR=.98), likewise the pricing policy has a protective effect on the four prevalence of alcohol consumption. ConclusionThe general perception of public policy, as well as the perception of harm reduction policies are predictor of alcohol consumption in young university students, therefore, these should be clear and widely known by this population, to facilitate compliance and have the expected effect.

Autophosphorylation of αCaMKII regulates alcohol consumption by controlling sedative effects of alcohol and alcohol-induced loss of excitatory synapses.

Calcium/calmodulin-dependent kinase II (CaMKII) is a key enzyme at the glutamatergic synapses. CAMK2A gene variants have been linked with alcohol use disorder (AUD) by an unknown mechanism. Here, we looked for the link between αCaMKII autophosphorylation and the AUD aetiology. Autophosphorylation-deficient heterozygous αCaMKII mutant mice (T286A+/- ) were trained in the IntelliCages to test the role of αCaMKII activity in AUD-related behaviours. The glutamatergic synapses morphology in CeA was studied in the animals drinking alcohol using 3D electron microscopy. We found that T286A+/- mutants consumed less alcohol and were more sensitive to sedating effects of alcohol, as compared to wild-type littermates (WT). After voluntary alcohol drinking, T286A+/- mice had less excitatory synapses in the CeA, as compared to alcohol-naive animals. This change correlated with alcohol consumption was not reversed after alcohol withdrawal and not observed in WT mice. Our study suggests that αCaMKII autophosphorylation affects alcohol consumption by controlling sedative effects of alcohol and preventing synaptic loss in the individuals drinking alcohol. This finding advances our understanding of the molecular processes that regulate alcohol dependence.

RGS6 negatively regulates inhibitory G protein signaling in dopamine neurons and positively regulates binge-like alcohol consumption in mice.

Drugs of abuse, including alcohol, increase dopamine in the mesocorticolimbic system via actions on dopamine neurons in the ventral tegmental area (VTA). Increased dopamine transmission can activate inhibitory G protein signalling pathways in VTA dopamine neurons, including those controlled by GABAB and D2 receptors. Members of the R7 subfamily of regulator of G protein signalling (RGS) proteins can regulate inhibitory G protein signalling, but their influence on VTA dopamine neurons is unclear. Here, we investigated the influence of RGS6, an R7 RGS family memberthat has been implicated in the regulation of alcohol consumption in mice, on inhibitory G protein signalling in VTA dopamine neurons. We used molecular, electrophysiological and genetic approaches to probe the impact of RGS6 on inhibitory G protein signalling in VTA dopamine neurons and on binge-like alcohol consumption in mice. RGS6 is expressed in adult mouse VTA dopamine neurons and it modulates inhibitory G protein signalling in a receptor-dependent manner, tempering D2 receptor-induced somatodendritic currents and accelerating deactivation of synaptically evoked GABAB receptor-dependent responses. RGS6-/- mice exhibit diminished binge-like alcohol consumption, a phenotype replicated in female (but not male) mice lacking RGS6 selectively in VTA dopamine neurons. RGS6 negatively regulates GABAB - and D2 receptor-dependent inhibitory G protein signalling pathways in mouse VTA dopamine neurons and exerts a sex-dependent positive influence on binge-like alcohol consumption in adult mice. As such, RGS6 may represent a new diagnostic and/or therapeutic target for alcohol use disorder.

Impaired Decision-Making and Skin Conductance Responses Are Associated with Reward and Punishment Sensitivity in Individuals with Severe Alcohol Use Disorder

Introduction: Individuals with alcohol use disorder (AUD) have difficulties regulating alcohol consumption, despite adverse drinking-related consequences. This may be due to incapacity incorporating previous negative feedback from drinking, resulting in impaired decision-making. Methods: We assessed whether decision-making is impaired in participants with AUD related to severity of AUD, indexed by severe negative drinking consequences using the Drinkers Inventory of Consequences (DrInC) and reward and punishment sensitivity with the Behavioural Inhibition System Behavioural Activation System (BIS BAS) scales. 36 treatment-seeking alcohol-dependent participants completed the Iowa gambling task (IGT) with skin conductance responses (SCRs) measured continuously as an index of somatic autonomic arousal to evaluate impaired expectancy of negative outcomes. Results: Two-thirds of the sample showed behavioural impairment during the IGT, with greater AUD severity related to worse performance. BIS moderated IGT performance according to severity of AUD, with increased anticipatory SCRs for those with fewer reported DrInC severe consequences. Participants with more DrInC severe consequences showed IGT deficits and reduced SCRs regardless of BIS scores. BAS-Reward was associated with increased anticipatory SCRs to disadvantageous deck choices among those with lower AUD severity, while SCRs did not differ related to AUD severity for reward outcomes. Discussion: Effective decision-making in the IGT and adaptive somatic responses were moderated by punishment sensitivity contingent on severity of AUD in these drinkers, with impairments in expectancy to negative outcomes from risky choices, including reduced somatic responses, resulting in poor decision-making processes that may help explain impaired drinking and worse drinking-related consequences.

Current Developments in European Alcohol Policy: An Analysis of Possible Impacts on the German Wine Industry

In February 2022, the European Parliament agreed on a far-reaching package of measures to regulate alcohol consumption in its vote on “Strengthening Europe in the fight against cancer”. This article therefore elaborates on the most important positions and directions of current European alcohol policy and discusses possible effects on the German wine industry based on existing literature. It can be shown that the attitudes towards alcohol consumption sometimes differ considerably within the European Union, but that there is increasing harmonization of consumption-regulating measures in the course of European integration. However, alcohol policies in the EU are limited by an unclear scientific assessment of “moderate” consumption. This is supplemented by moderate social awareness and the scientific discourse on the effectiveness of alcohol policy measures, as well as a lack of government initiative and legal barriers. Ultimately, the German wine industry finds itself confronted with new scientific findings, associated political demands and creeping changes in social attitudes towards alcoholic beverages.

Executive Dysfunction in Patients With Alcohol Use Disorder: A Systematic Review.

A medical condition known as alcohol use disorder (AUD) is defined as an impaired capacity to reduce or regulate alcohol consumption despite negative social, occupational, or health effects. According to studies, habitual drinkers experience a reduction in their capacity to process new information, gain new skills, and formulate plans. Studies indexed in PubMed, PubMed Central, Google Scholar, ResearchGate, and ScienceDirect, published from 2012 to 2022, were identified through the search terms “alcohol use disorder” and “executive function.” A total of 2242 abstracts were identified through the initial search terms. Full texts were reviewed for 61 articles, out of which nine articles met the criteria for inclusion. This systematic review was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The current systematic review primarily focuses on the following issues: clinical neuropsychological tests of executive dysfunction, specific brain regions most affected by alcohol neurotoxic effects, and alcohol-related dementia. This review concluded that chronic alcohol dependence syndrome causes impairments in several cognitive function domains. Study shows frontal lobe damage is caused by chronic alcohol consumption. A faulty interaction among large-scale networks underlies patients' executive dysfunction in AUD, which is suggested by changes in prefrontal white-matter pathways. The goal of this systematic review is to improve the ability to recognize alcoholics who are particularly at risk of functional impairments to tailor therapeutic therapy to maximize the chance of maintaining abstinence and neuropsychology concerning this complex disease.

The problem of alcohol consumption and the prerequisites of alcoholism development in medical students

In many parts of the world, alcohol use, especially among young people, is a growing concern. Excessive alcohol consumption has a negative impact on various social aspects of life, social well-being and economic development in general, leading to the development of a range of mental and physical diseases, as well as causing injuries from road traffic accidents, suicide attempts and acts of violence. The results of an anonymous survey among students of the Saratov State Medical University named after V.I. Razumovsky of the Ministry of Health of Russia showed that despite sufficient awareness of the dangers of alcohol, young people continue to drink alcoholic beverages. This fact confirms the need for state regulation of alcohol consumption at the national and global levels. The harmful effects of alcohol consumption among young people can be reduced through the use of proven technologies and strategies for the prevention of alcohol dependence on the part of the state and society.

Orbitofrontal cortex subregion inhibition during binge-like and aversion-resistant alcohol drinking.

Two important contributors to alcohol-related problems and alcohol use disorder (AUD) are binge- and compulsive-like drinking. The orbitofrontal cortex (OFC), a brain region implicated in outcome valuation and behavioral flexibility, is functionally altered by alcohol exposure. Data from animal models also suggest that both the medial (mOFC) and lateral (lOFC) subregions of the OFC regulate alcohol-related behaviors. The current study was designed to examine the contributions of mOFC and lOFC using a model of binge-like and aversion-resistant ethanol drinking in C57BL/6J male and female mice. The inhibitory Designer Receptor Exclusively Activated by Designer Drugs (DREADD) hM4Di were used to inhibit neurons in either the mOFC or the lOFC in mice drinking 15% ethanol in a two-bottle, limited-access, modified drinking in the dark paradigm. The effects of chemogenetic inhibition on consumption of quinine-adulterated ethanol, water, and water+quinine were also assessed. Inhibiting the mOFC did not alter consumption of ethanol or aversion-resistant drinking of ethanol+quinine. In contrast, inhibition of neurons in the lOFC increased consumption, but not preference, of ethanol alone. mOFC and lOFC inhibition did not alter water or quinine-adulterated water intake, indicating the effects shown here are specific to ethanol drinking. These data support the role of the lOFC in regulating alcohol consumption but fail to find a similar role for mOFC.

Youths' Perceptions Of The Relation Between Alcohol Consumption And Risky Sexual Behaviour in the Western Cape, South Africa: A Qualitative Study.

The purpose of this study is to explore the factors that youth identify as contributing to alcohol consumption, and more specifically its relation to risky sexual behaviour among youth. We employed an exploratory qualitative method using focus group discussions with 34 young people between the ages of 18-25-years-old in low socio-economic status communities in the Western Cape province of South Africa. Data were analyzed thematically utilizing Braun and Clarke’s (2006) six-step thematic analysis process. We identified two thematic domains pertaining to alcohol consumption and risky sexual behaviour, namely individual and social factors, each comprising three themes. The individual factors thematic domain comprises intrapersonal influences, employment and educational attainment; while the social factors thematic domain includes interpersonal influences, social influences, and hope for the future. Youth living in low socio-economic status communities were thought to be at greater risk of alcohol misuse and subsequent risky behaviour, given the political and social history of marginalisation, systematic oppression, and social inequality. To address alcohol use and risky sexual behavior among youth, we recommend interventions with adolescents, parents or guardians, and the community. More specifically, interventions aimed at adolescents should focus on the transition to young adulthood. Interventions with parents should focus on their role in modelling and potentially regulating alcohol consumption. Finally, community interventions should centre on drinking behaviors, levels of drinking, what constitutes harmful drinking, and how to identify when treatment and recovery support is likely to be required.

Vesicular glutamate transporter 2-containing neurons of the centrally-projecting Edinger-Westphal nucleus regulate alcohol drinking and body temperature

Previous studies in rodents have repeatedly demonstrated that the centrally-projecting Edinger-Westphal nucleus (EWcp) is highly sensitive to alcohol and is also involved in regulating alcohol intake and body temperature. Historically, the EWcp has been known as the main site of Urocortin 1 (Ucn1) expression, a corticotropin-releasing factor-related peptide, in the brain. However, the EWcp also contains other populations of neurons, including neurons that express the vesicular glutamate transporter 2 (Vglut2). Here we transduced the EWcp with adeno-associated viruses (AAVs) encoding Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) to test the role of the EWcp in alcohol drinking and in the regulation of body temperature. Activation of the EWcp with excitatory DREADDs inhibited alcohol intake in a 2-bottle choice procedure in male C57BL/6J mice, whereas inhibition of the EWcp with DREADDs had no effect. Surprisingly, analysis of DREADD expression indicated Ucn1-containing neurons of the EWcp did not express DREADDs. In contrast, AAVs transduced non-Ucn1-containing EWcp neurons. Subsequent experiments showed that the inhibitory effect of EWcp activation on alcohol intake was also present in male Ucn1 KO mice, suggesting that a Ucn1-devoid population of EWcp regulates alcohol intake. A final set of chemogenetic experiments showed that activation of Vglut2-expressing EWcp neurons inhibited alcohol intake and induced hypothermia in male and female mice. These studies expand on previous literature by indicating that a glutamatergic, Ucn1-devoid subpopulation of the EWcp regulates alcohol consumption and body temperature.

Somatostatin neurons control an alcohol binge drinking prelimbic microcircuit in mice

Somatostatin (SST) neurons have been implicated in a variety of neuropsychiatric disorders such as depression and anxiety, but their role in substance use disorders, including alcohol use disorder (AUD), is not fully characterized. Here, we found that repeated cycles of alcohol binge drinking via the Drinking-in-the-Dark (DID) model led to hypoactivity of SST neurons in the prelimbic (PL) cortex by diminishing their action potential firing capacity and excitatory/inhibitory transmission dynamic. We examined their role in regulating alcohol consumption via bidirectional chemogenetic manipulation. Both hM3Dq-induced excitation and KORD-induced silencing of PL SST neurons reduced alcohol binge drinking in males and females, with no effect on sucrose consumption. Alcohol binge drinking disinhibited pyramidal neurons by augmenting SST neurons-mediated GABA release and synaptic strength onto other GABAergic populations and reducing spontaneous inhibitory transmission onto pyramidal neurons. Pyramidal neurons additionally displayed increased intrinsic excitability. Direct inhibition of PL pyramidal neurons via hM4Di was sufficient to reduce alcohol binge drinking. Together these data revealed an SST-mediated microcircuit in the PL that modulates the inhibitory dynamics of pyramidal neurons, a major source of output to subcortical targets to drive reward-seeking behaviors and emotional response.

Sex-specific plasticity in CRF regulation of inhibitory control in central amygdala CRF1 neurons after chronic voluntary alcohol drinking.

Despite strong preclinical evidence for the ability of corticotropin releasing factor 1 (CRF1) antagonists to regulate alcohol consumption, clinical trials have not yet demonstrated therapeutic effects of these compounds in alcohol use disorder (AUD) patients. Several confounding factors may limit the translation of preclinical CRF1 research to patients, including reliance on experimenter-administered alcohol instead of voluntary consumption, a preponderance of evidence collected in male subjects only and an inability to assess the effects of alcohol on specific brain circuits. A population of particular interest is the CRF1-containing neurons of the central amygdala (CeA). CRF1 CeA neurons are sensitive to ethanol, but the effects of alcohol drinking on CRF signalling within this population are unknown. In the present study, we assessed the effects of voluntary alcohol drinking on inhibitory control of CRF1+ CeA neurons from male and female CRF1:GFP mice using ex vivo electrophysiology and determined the contributions of CRF1 signalling to inhibitory control and voluntary alcohol drinking. Chronic alcohol drinking produced neuroadaptations in CRF1+ neurons that increased the sensitivity of GABAA receptor-mediated sIPSCs to the acute effects of alcohol, CRF and the CRF1 antagonist R121919, but these adaptations were more pronounced in male versus female mice. The CRF1 antagonist CP-154,526 reduced voluntary alcohol drinking in both sexes and abolished sex differences in alcohol drinking. The lack of alcohol-induced adaptation in the female CRF1 system may be related to the elevated alcohol intake exhibited by female mice and could contribute to the ineffectiveness of CRF1 antagonists in female AUD patients.

Travels and Travails of Settler Colonialism in Queer Natal

Travels and Travails of Settler Colonialism in Queer Natal