Alcohol Preference Research Articles

Alcohol and Vaporized Nicotine Co-exposure During Adolescence Contribute Differentially to Sex-Specific Behavioral Effects in Adulthood.

Co-occurrence of e-cigarette use and alcohol consumption during adolescence is frequent. Here, we examined whether adolescent co-exposure to alcohol drinking and vaporized nicotine would impact reward- and cognition-related behaviors in adult male and female rats during adulthood. Four groups of male and female Sprague Dawley rats (n = 8-11/group/sex) received either nicotine (JUUL 5% nicotine pods) or vehicle vapor for 10 minutes daily between postnatal days 30-46, while having continuous voluntary access to ethanol and water during this time in a two-bottle preference design. Upon reaching adulthood, all rats underwent behavioral testing (ie, Pavlovian conditioned approach testing, fear conditioning and a two-bottle alcohol preference). A sex-dependent effect, not related to adolescent nicotine or alcohol exposure, on alcohol drinking in adulthood was found, such that females had a higher intake and preference for alcohol compared to males; both male and female adult rats also had greater alcohol preference compared to their alcohol preference as adolescents. Male rats exposed to vaporized nicotine with or without alcohol drinking during adolescence exhibited altered reward-related learning in adulthood, evidenced by enhanced levels of sign-tracking behavior. Male rats that drank alcohol with or without nicotine vapor in adolescence showed deficits in associative fear learning and memory as adults. In contrast, these effects were not seen in female rats exposed to alcohol and nicotine vapor during adolescence. The present study provides evidence that co-exposure to alcohol and vaporized nicotine during adolescence in male, but not female, rats produces long-term changes in reward- and cognition-related behaviors. These findings enhance our understanding of the effects of alcohol drinking and nicotine vapor exposure in adolescence. Moreover, they highlight potential sex differences that exist in the response to alcohol and nicotine vapor, underscoring the need for follow-up studies elucidating the neurobiological mechanisms that drive these sex differences, as well as the long-term effects of alcohol and nicotine vapor use.

The oral microbiome in alcohol use disorder: a longitudinal analysis during inpatient treatment

ABSTRACT Background Alcohol use disorder (AUD)-induced disruption of oral microbiota can lead to poor oral health; there have been no studies published examining the longitudinal effects of alcohol use cessation on the oral microbiome. Aim To investigate the oral microbiome during alcohol cessation during inpatient treatment for AUD. Methods Up to 10 oral tongue brushings were collected from 22 AUD patients during inpatient treatment at the National Institutes of Health. Alcohol use history, smoking, and periodontal disease status were measured. Oral microbiome samples were sequenced using 16S rRNA gene sequencing. Results Alpha diversity decreased linearly during treatment across the entire cohort (P = 0.002). Alcohol preference was associated with changes in both alpha and beta diversity measures. Characteristic tongue dorsum genera from the Human Microbiome Project such as Streptococcus, Prevotella, Veillonella and Haemophilus were highly correlated in AUD. Oral health-associated genera that changed longitudinally during abstinence included Actinomyces, Capnocytophaga, Fusobacterium, Neisseria and Prevotella. Conclusion The oral microbiome in AUD is affected by alcohol preference. Patients with AUD often have poor oral health but abstinence and attention to oral care improve dysbiosis, decreasing microbiome diversity and periodontal disease-associated genera while improving acute oral health.

Effect of ketamine on binge drinking patterns in crossed high alcohol-preferring (cHAP) mice.

Previous research has demonstrated the utility of subanesthetic doses of ketamine in decreasing binge (Drinking-in-the-Dark, or DID) 20% alcohol intake in female inbred (C57BL/6J) mice when administered 12 hours prior to alcohol access (Crowley etal., 2019). In the current study, we assess the efficacy of a similar ketamine pretreatment using male and female selectively bred, crossed High Alcohol Preferring (cHAP) mice, which also drink to intoxication, but are not inbred. We hypothesized that ketamine would decrease binge alcohol intake without impacting locomotor activity. Subjects were 28 adult cHAP mice. Mice first received a 2-week DID drinking history using 2-h/day alcohol access. On day 12, prior to ketamine treatment, the average blood ethanol concentration (BEC) was 130mg/dL, confirming that mice reliably reached intoxicating BECs. On day 15, mice were given 0, 3, or 10mg/kg of ketamine 12 hours prior to the DID session. Ketamine did not decrease total (2-h) alcohol consumption or locomotion. Interestingly, the 10mg/kg dose of ketamine did alter the drinking pattern in male mice, decreasing front-loading for a single day. We opted to then increase the doses to 32 or 100mg/kg (i.e., an anesthetic dose) two days after the initial treatment, keeping the saline control. Mice of both sexes decreased total binge alcohol intake at the 100mg/kg dose only, but again, the effect only lasted one day. The current study found that cHAP mice reached more than double the BECs observed in C57BL/6J mice during DID, but did not respond to subanesthetic ketamine. Modest efficacy was found for ketamine pretreatment at anesthetic doses. Differences in findings may be due to differential intake during DID, or genetic differences between C57Bl/6J mice and cHAP mice. Drug efficacy in multiple models is important for discovering reliable pharmacotherapies for alcoholism.

The impact of intermittent exercise on mouse ethanol drinking and abstinence-associated affective behavior and physiology.

Negative emotional states are associated with the initiation and maintenance of alcohol use and drive relapse to drinking during withdrawal and protracted abstinence. Physical exercise is correlated with decreased negative affective symptoms, although a direct relationship between drinking patterns and exercise level has not been fully elucidated. We incorporated intermittent running wheel access into a chronic continuous access, two-bottle choice alcohol drinking model in female C57BL/6J mice. Wheel access was granted intermittently once mice established a preference for alcohol over water. After 6weeks, alcohol was removed (forced abstinence) and mice were given continuous access to unlocked or locked wheels. Negative affect-like behavior, home cage behavior, and metabolic activity were measured during protracted abstinence. Wheel access shifted drinking patterns in the mice, increasing drinking when the wheel was locked, and decreasing drinking when unlocked. Moreover, alcohol preference and consumption were strongly negatively correlated with the amount of running. An assessment of negative affect-like behavior in abstinence via the novelty suppressed feeding and saccharin preference tests (SPT) showed that unlimited wheel access mitigated abstinence-induced latency increases. Mice in abstinence also spent more time sleeping during the active dark cycle than control mice, providing additional evidence for abstinence-induced anhedonia- and depression-like behavior. Furthermore, running wheel access in abstinence decreased dark cycle sleep to comparable alcohol- and wheel-naïve mice. Given the positive impact of exercise and the negative impact of alcohol on metabolic health, we compared metabolic phenotypes of alcohol-abstinent mice with and without wheel access. Wheel access increased energy expenditure, carbon dioxide production, and oxygen consumption, providing a potential metabolic mechanism through which wheel access improves affective state. This study suggests that including exercise in AUD treatment regimens has the potential to reduce drinking, improve affective state during abstinence and could serve as a non-pharmacological approach to prevent the development of an AUD in high-risk individuals.

Variations of Brain Functional Connectivity in Alcohol-Preferring and Non-Preferring Rats with Consecutive Alcohol Training or Acute Alcohol Administration.

Alcohol addiction is regarded as a series of dynamic changes to neural circuitries. A comparison of the global network during different stages of alcohol addiction could provide an efficient way to understand the neurobiological basis of addiction. Two animal models (P-rats screened from an alcohol preference family, and NP-rats screened from an alcohol non-preference family) were trained for alcohol preference with a two-bottle free choice method for 4 weeks. To examine the changes in the neural response to alcohol during the development of alcohol preference and acute stimulation, different trials were studied with resting-state fMRI methods during different periods of alcohol preference. The correlation coefficients of 28 regions in the whole brain were calculated, and the results were compared for alcohol preference related to the genetic background/training association. The variety of coherence patterns was highly related to the state and development of alcohol preference. We observed significant special brain connectivity changes during alcohol preference in P-rats. The comparison between the P- and NP-rats highlighted the role of genetic background in alcohol preference. The results of this study support the alterations of the neural network connection during the formation of alcohol preference and confirm that alcohol preference is highly related to the genetic background. This study could provide an effective approach for understanding the neurobiological basis of alcohol addiction.

Mice with high FGF21 serum levels had a reduced preference for morphine and an attenuated development of acute antinociceptive tolerance and physical dependence

Because of increased opioid misuse, there is a need to identify new targets for minimizing opioid tolerance, and physical and psychological dependence. Previous studies showed that fibroblast growth factor 21 (FGF21) decreased alcohol and sweet preference in mice. In this study, FGF21-transgenic (FGF21-Tg) mice, expressing high FGF21 serum levels, and wildtype (WT) C57BL/6J littermates were treated with morphine and saline to determine if differences exist in their physiological and behavioral responses to opioids. FGF21-Tg mice displayed reduced preference for morphine in the conditioned place preference assay compared to WT littermates. Similarly, FGF21-Tg mice had an attenuation of the magnitude and rate of acute morphine antinociceptive tolerance development, and acute and chronic morphine physical dependence, but exhibited no change in chronic morphine antinociceptive tolerance. The ED50 values for morphine-induced antinociception in the 55 °C hot plate and the 55 °C warm-water tail withdrawal assays were similar in both strains of mice. Likewise, FGF21-Tg and WT littermates had comparable responses to morphine-induced respiratory depression. Overall, FGF21-Tg mice had a decrease in the development of acute analgesic tolerance, and the development of physical dependence, and morphine preference. FGF21 and its receptor have therapeutic potential for reducing opioid withdrawal symptoms and craving, and augmenting opioid therapeutics for acute pain patients to minimize tolerance development.

Bmal1 in the striatum influences alcohol intake in a sexually dimorphic manner

Alcohol consumption has been strongly associated with circadian clock gene expression in mammals. Analysis of clock genes revealed a potential role of Bmal1 in the control of alcohol drinking behavior. However, a causal role of Bmal1 and neural pathways through which it may influence alcohol intake have not yet been established. Here we show that selective ablation of Bmal1 (Cre/loxP system) from medium spiny neurons of the striatum induces sexual dimorphic alterations in alcohol consumption in mice, resulting in augmentation of voluntary alcohol intake in males and repression of intake in females. Per2mRNA expression, quantified by qPCR, decreases in the striatum after the deletion of Bmal1. To address the possibility that the effect of striatal Bmal1 deletion on alcohol intake and preference involves changes in the local expression of Per2, voluntary alcohol intake (two-bottle, free-choice paradigm) was studied in mice with a selective ablation of Per2 from medium spiny neurons of the striatum. Striatal ablation of Per2 increases voluntary alcohol intake in males but has no effect in females. Striatal Bmal1 and Per2 expression thus may contribute to the propensity to consume alcohol in a sex -specific manner in mice.

Changes in Brain Dopamine Extracellular Concentration after Ethanol Administration; Rat Microdialysis Studies.

The purpose of this review is to evaluate microdialysis studies where alterations in the dopaminergic system have been evaluated after different intoxication states, in animals showing preference or not for alcohol, as well as during alcohol withdrawal. Ethanol administration induces varying alterations in dopamine microdialysate concentrations, thereby modulating the functional output of the dopaminergic system. Administration of low doses of ethanol, intraperitoneally, intravenously, orally or directly into the nucleus accumbens, NAc, increases mesolimbic dopamine, transmission, as shown by increases in dopamine content. Chronic alcohol administration to rats, which show alcohol-dependent behaviour, induced little change in basal dopamine microdialysis content. In contrast, reduced basal dopamine content occurred after ethanol withdrawal, which might be the stimulus to induce alcohol cravings and consumption. Intermittent alcohol consumption did not identify any consistent changes in dopamine transmission. Animals which have been selectively or genetically bred for alcohol preference did not show consistent changes in basal dopamine content although, exhibited a significant ethanol-evoked dopamine response by comparison to non-preference animals. Microdialysis has provided valuable information about ethanol-evoked dopamine release in the different animal models of alcohol abuse. Acute ethanol administration increases dopamine transmission in the rat NAc whereas chronic ethanol consumption shows variable results which might reflect whether the rat is prior to or experiencing ethanol withdrawal. Ethanol withdrawal significantly decreases the extracellular dopamine content. Such changes in dopamine surges will contribute to both drug dependence, e.g. susceptibility to drug withdrawal, and addiction, by compromising the ability to react to normal dopamine fluctuations.

Sex and context differences in the effects of trauma on comorbid alcohol use and post-traumatic stress phenotypes in actively drinking rats.

Alcohol use disorder (AUD) and affective disorders are frequently comorbid and share underlying mechanisms that could be targets for comprehensive treatment. Post-traumatic stress disorder (PTSD) has high comorbidity with AUD, but comprehensive models of this overlap are nascent. We recently characterized a model of comorbid AUD and PTSD-like symptoms, wherein stressed rats receive an inhibitory avoidance (IA)-related footshock on two occasions followed by two-bottle choice (2BC) voluntary alcohol drinking. Stressed rats received the second footshock in a familiar (FAM, same IA box as the first footshock) or novel context (NOV, single-chambered apparatus); the FAM paradigm more effectively increased alcohol drinking in males and the NOV paradigm in females. During abstinence, stressed males displayed avoidance-like PTSD symptoms, and females showed hyperarousal-like PTSD symptoms. Rats in the model had altered spontaneous action potential-independent GABAergic transmission in the central amygdala (CeA), a brain region key in alcohol dependence and stress-related signaling. However, PTSD sufferers may have alcohol experience prior to their trauma. Here, we therefore modified our AUD/PTSD comorbidity model to provide 3weeks of intermittent extended alcohol access before footshock and then studied the effects of NOV and FAM stress on drinking and PTSD phenotypes. NOV stress suppressed the escalation of alcohol intake and preference seen in male controls, but no stress effects were seen on drinking in females. Additionally, NOV males had decreased action potential-independent presynaptic GABA release and delayed postsynaptic GABAA receptor kinetics in the CeA compared to control and FAM males. Despite these changes to alcohol intake and CeA GABA signaling, stressed rats showed broadly similar anxiogenic-like behaviors to our previous comorbid model, suggesting decoupling of the PTSD symptoms from the AUD vulnerability for some of these animals. The collective results show the importance of alcohol history and trauma context in vulnerability to comorbid AUD/PTSD-like symptoms.

Circadian gene × environment perturbations influence alcohol drinking in Cryptochrome-deficient mice.

Alcohol use disorder (AUD) is a widespread addiction disorder with severe consequences for health. AUD patients often suffer from sleep disturbances and irregular daily patterns. Conversely, disruptions of circadian rhythms are considered a risk factor for AUD and alcohol relapses. In this study, we investigated the extent to which circadian genetic and environmental disruptions and their interaction alter alcohol drinking behaviour in mice. As a model of genetic circadian disruption, we used Cryptochrome1/2-deficient (Cry1/2-/- ) mice with strongly suppressed circadian rhythms and found that they exhibit significantly reduced preference for alcohol but increased incentive motivation to obtain it. Similarly, we found that low circadian SCN amplitude correlates with reduced alcohol preference in WT mice. Moreover, we show that the low alcohol preference of Cry1/2-/- mice concurs with high corticosterone and low levels of the orexin precursor prepro-orexin and that WT and Cry1/2-/- mice respond differently to alcohol withdrawal. As a model of environmentally induced disruption of circadian rhythms, we exposed mice to a "shift work" light/dark regimen, which also leads to a reduction in their alcohol preference. Interestingly, this effect is even more pronounced when genetic and environmental circadian perturbations interact in Cry1/2-/- mice under "shift work" conditions. In conclusion, our study demonstrates that in mice, disturbances in circadian rhythms have pronounced effects on alcohol consumption as well as on physiological factors and other behaviours associated with AUD and that the interaction between circadian genetic and environmental disturbances further alters alcohol consumption behaviour.

Effects of sex and genotype in human APOE-targeted replacement mice on alcohol self-administration measured with the automated IntelliCage system before and after repeated mild traumatic brain injury.

Few studies have examined the association between APOE genotype and alcohol use. Although some of these studies have reported outcomes associated with a history of drinking, none have examined alcohol-seeking behavior. In addition, no preclinical studies have examined alcohol use as a function of APOE genotype with or without traumatic brain injury. Male and female human APOE3- and APOE4-targeted replacement (TR) mice were used to assess voluntary alcohol seeking longitudinally using a 2-bottle choice paradigm conducted within the automated IntelliCage system prior to and following repeated mild TBI (rmTBI). Following an acquisition phase in which the concentration of ethanol (EtOH) was increased to 12%, a variety of drinking paradigms that included extended alcohol access (EAA1 and EAA2), alcohol deprivation effect (ADE), limited access drinking in the dark (DID), and progressive ratio (PR) were used to assess alcohol-seeking behavior. Additional behavioral tasks were performed to measure cognitive function and anxiety-like behavior. All groups readily consumed increasing concentrations of EtOH (4-12%) during the acquisition phase. During the EAA1 period (12% EtOH), there was a significant genotype effect in both males and females for EtOH preference. Following a 3-week abstinence period, mice received sham or rmTBI resulting in a genotype- and sex-independent main effect of rmTBI on the recovery of righting reflex and a main effect of rmTBI on spontaneous home-cage activity in females only. Reintroduction of 12% EtOH (EAA2) resulted in a significant effect genotype for alcohol preference in males with APOE4mice displaying increased preference and motivation for alcohol compared with APOE3mice independent of TBI while in females, there was a significant genotype×TBI interaction under the ADE and DID paradigms. Finally, there was a main effect of rmTBI on increased risk-seeking behavior in both sexes, but no effect on spatial learning or cognitive flexibility. These results suggest that sex and APOE genotype play a significant role in alcohol consumption and may subsequently influence long-term recovery following traumatic brain insults.

Blockade of GPR55 in dorsal periaqueductal gray produces anxiety-like behaviors and evocates defensive aggressive responses in alcohol-pre-exposed rats

GPR55 is a receptor expressed in several central nervous system areas, including the periaqueductal gray (PAG). Current knowledge of GPR55 physiology in PAG only covers pain integration, but it is involved in other actions such as anxiety, panic, motivated behaviors, and alcohol intake. In the present study, juvenile male Wistar rats were unexposed (alcohol-naïve group; A-naïve) or exposed to alcohol for 5 weeks (alcohol-pre-exposed group; A-pre-exposed). Posteriorly, animals received intra dorsal-PAG (D-PAG) injections of vehicle (10% DMSO), LPI (1 nmol/0.5 µl) and ML-193 (1 nmol/0.5 µl, a selective GPR55 antagonist). Finally, defensive burying behavior (DBB) paradigm and alcohol preference were evaluated. Compared to the A-naïve group, the A-pre-exposed vehicle group had higher (p < 0.05): (i) time of immobility; (ii) latency to and duration of burying; and (iii) alcohol consumption. In both groups (i.e., A-naïve and A-pre-exposed) treatment with LPI: (i) decreased duration of burying (p < 0.05); (ii) suppressed time of immobility; and (iii) increased alcohol intake (p < 0.05). On the other hand, treatment with ML-193: (i) decreased duration of immobility in A-pre-exposed (but not in A-naïve rats); (ii) promoted an aggressive response against the shock-probe in A-pre-exposed rats (p < 0.05); and (iii) increased alcohol intake (p < 0.05). Our results suggest that blockade of GPR55 in D-PAG is associated with anxiety-like behaviors, defensive aggressive behaviors, and higher alcohol intake, whereas LPI in D-PAG produced anxiolytic-like effects (probably GPR55-mediated), but not prevention of alcohol intake.

Voluntary Adolescent-Onset Alcohol Drinking Fails to Influence Alcohol Consumption or Anxiety-Like Behaviour in Adulthood in Female Alcohol-Preferring Rats.

AimsAlcohol exposure during adolescence is associated with both increased risk for alcohol use disorders and anxiety in adulthood. Our present experiments examined this association using alcohol-preferring AA (Alko Alcohol) rats selected for high voluntary alcohol drinking.MethodsTwo groups of female AA rats acquired alcohol drinking at different ages. We gave the adolescent-onset group free choice to 10% alcohol and water for seven weeks, starting on post-natal day 42 (PND 42), whereas the adult-onset group started drinking alcohol on PND 112. After the 7-week drinking, we withdrew the adolescent group from alcohol for two weeks, followed by another voluntary 7-week drinking period, started at the same age as the adult-onset group. We assessed anxiety-like behaviour repeatedly during alcohol drinking with open field and elevated plus maze tests. At the end of alcohol drinking, we also tested the rats using the light/dark box, stress-induced body temperature test and social dominance test.ResultsDuring the first 7-week alcohol drinking, adolescent rats exhibited significantly slower acquisition of alcohol drinking and lower alcohol preference than the adult-onset group. However, when tested at the same age as the adult-onset rats, they displayed identical alcohol intake and preference. We found no alcohol-induced effects on anxiety- or stress-related behaviour in the experimental groups at any time points.ConclusionsThese data show that the genetically determined phenotype of high alcohol drinking of the female alcohol-preferring AA rats is not associated with a predisposition to develop anxiety-like behaviour following voluntary alcohol exposure, even when initiated during adolescence.

Acetaldehyde Enhances Alcohol Sensitivity and Protects against Alcoholism: Evidence from Alcohol Metabolism in Subjects with Variant ALDH2*2 Gene Allele.

Alcoholism is a complex behavior trait influenced by multiple genes as well as by sociocultural factors. Alcohol metabolism is one of the biological determinants that can significantly influence drinking behaviors. Alcohol sensitivity is thought to be a behavioral trait marker for susceptibility to develop alcoholism. The subjective perceptions would be an indicator for the alcohol preference. To investigate alcohol sensitivity for the variants ADH1B*2 and ALDH2*2, sixty healthy young males with different combinatory ADH1B and ALDH2 genotypes, ADH1B*2/*2–ALDH2*1/*1 (n = 23), ADH1B*2/*2–ALDH2*1/*2 (n = 27), and ADH1B*1/*1–ALDH2*1/*1 (n = 10), participated in the study. The subjective perceptions were assessed by a structured scale, and blood ethanol and acetaldehyde were determined by GC and HPLC after an alcohol challenge in two dose sessions (0.3 g/kg or 0.5 g/kg ethanol). The principal findings are (1) dose-dependent increase of blood ethanol concentration, unaffected by ADH1B or ALDH2; (2) significant build-up of blood acetaldehyde, strikingly influenced by the ALDH2*2 gene allele and correlated with the dose of ingested alcohol; (3) the increased heart rate and subjective sensations caused by acetaldehyde accumulation in the ALDH2*2 heterozygotes; (4) no significant effect of ADH1B polymorphism in alcohol metabolism or producing the psychological responses. The study findings provide the evidence of acetaldehyde potentiating the alcohol sensitivity and feedback to self-control the drinking amount. The results indicate that ALDH2*2 plays a major role for acetaldehyde-related physiological negative responses and prove the genetic protection against development of alcoholism in East Asians.

Antagonism of Sigma-1 receptor blocks heavy alcohol drinking and associated hyperalgesia in male mice.

Alcohol use disorder (AUD) is a complex psychiatric disease characterized by high alcohol intake as well as hyperkatifeia and hyperalgesia during withdrawal. A role for Sigma-1 receptors (Sig-1Rs) in the rewarding and reinforcing effects of alcohol has started to emerge in recent years, as rat studies have indicated that Sig-1R hyperactivity may result in excessive alcohol drinking. Sig-1R studies in mice are very scarce, and its potential role in alcohol-induced hyperalgesia is also unknown. In this study, we investigated the role of Sig-1R in alcohol drinking and associated hyperalgesia in male mice, using an intermittent access 2-bottle choice model of heavy drinking. The Sig-1R antagonist BD-1063 was found dose dependently to reduce both alcohol intake and preference, without affecting either water or sucrose intake, suggesting that the effects are specific for alcohol. Notably, the ability of BD-1063 to suppress ethanol intake correlated with the individual baseline levels of alcohol drinking, suggesting that the treatment was more efficacious in heavy drinking animals. In addition, BD-1063 reversed alcohol-induced hyperalgesia during withdrawal, assessed using an automatic Hargreaves test, without affecting thermal sensitivity in alcohol-naïve animals or locomotor activity in either group. These data show that Sig-1R antagonism dose-dependently reduced ethanol consumption in heavy drinking mice as well as its efficacy in reducing alcohol-induced hyperalgesia. These findings provide a foundation for the development of novel treatments for AUD and associated pain states.

Effects of chronic voluntary alcohol consumption on PDE10A availability: a longitudinal behavioral and [18F]JNJ42259152 PET study in rats.

Phosphodiesterase 10A (PDE10A) is a dual substrate enzyme highly enriched in dopamine-receptive striatal medium spiny neurons, which are involved in psychiatric disorders such as alcohol use disorders (AUD). Although preclinical studies suggest a correlation of PDE10A mRNA expression in neuronal and behavioral responses to alcohol intake, little is known about the effects of alcohol exposure on in vivo PDE10A activity in relation to apparent risk factors for AUD such as decision-making and anxiety. We performed a longitudinal [18F]JNJ42259152 microPET study to evaluate PDE10A changes over a 9-week intermittent access to alcohol model, including 6weeks of alcohol exposure, 2weeks of abstinence followed by 1week relapse. Parametric PDE10A-binding potential (BPND) images were generated using a Logan reference tissue model with cerebellum as reference region and were analyzed using both a volume-of-interest and voxel-based approach. Moreover, individual decision-making and anxiety levels were assessed with the rat Iowa Gambling Task and open-field test over the IAE model. We observed an increased alcohol preference especially in those animals that exhibited poor initial decision-making. The first 2weeks of alcohol exposure resulted in an increased striatal PDE10A binding (> 10%). Comparing PDE10A-binding potential after 2 versus 4weeks of exposure showed a significant decreased PDE10A in the caudate-putamen and nucleus accumbens (pFWE-corrected < 0.05). This striatal PDE10A decrease was related to alcohol consumption and preference. Normalization of striatal PDE10A to initial levels was observed after 1week of relapse, apart from the globus pallidus. This study shows that chronic voluntary alcohol consumption induces a reversible increased PDE10A enzymatic availability in the striatum, which is related to the amount of alcohol preference. Thus, PDE10A-mediated signaling plays an important role in modulating the reinforcing effects of alcohol, and the data suggest that PDE10A inhibition may have beneficial behavioral effects on alcohol intake.

Expression of the hippocampal PTCH during early abstinence is associated with drinking patterns in a rat model of voluntary alcohol intake.

Perinatal alcohol exposure induces fetal alcohol syndrome partially through Sonic Hedgehog (SHH) impairment; however, the relationship between SHH signaling cascade and alcohol drinking pattern in adulthood remains obscure. We studied the expression of SHH and components of respective signaling cascade [PTCH receptor (Patched), SMO co-receptor (Smoothened) and downstream transcriptional factor Glioma-associated oncogene (GLI)] during early abstinence in brain regions of rats demonstrating different drinking patterns in intermittent access two-bottle choice paradigm (IA2BC). Male Wistar rats were subjected to twenty 24-h sessions of free access to two-bottle choice (water or 20% ethanol) with 24-h withdrawal periods (water only). Control animals had access to water only. Quantitative PCR and western blotting were used to assess transcript and protein levels in the brain, respectively. During the course of the IA2BC, one part of animals demonstrated gradual escalation from low to high alcohol intake and preference of alcohol over water (group I), while the other one consumed alcohol at stable high level (group II) (Peregud et al., 2021). Three days after the last drinking session, PTCH mRNA elevated in the hippocampus of group I rats as compared to the control group. However, SHH, SMO and GLI mRNA levels in the hippocampus did not change. The protein content of PTCH in the hippocampus of group I rats was higher as compared to both control and group II. PTCH elevation is a known marker of SHH cascade activity. Thus, activated hippocampal SHH signaling cascade is a hallmark of rats demonstrating gradual escalation of alcohol intake in the IA2BC procedure.

Self-Rated Aversion to Taste Qualities and the PROP Taster Phenotype Associate with Alcoholic Beverage Intake and Preference

Consumers often identify “taste” as an important factor when selecting alcoholic beverages. Although it is assumed that reduced alcohol consumption in PROP super-tasters is due to a greater dislike of the nominally aversive sensations that they experience more intensely (e.g., bitterness) when compared to PROP non-tasters, this question has not been specifically asked to them. Therefore, we examined consumers’ self-reported aversion towards specific sensory attributes (bitter, hot/burn, dry, sour, sweet, carbonation) for four alcoholic beverage types (white wine, red wine, beer, spirits) using a convenience sample of U.S. wine consumers (n = 925). Participants rated 18 statements describing different combinations of sensory attributes and alcoholic beverages on a 5-point Likert scale (e.g., Beer tastes too bitter for me). Individuals who tended to agree more strongly with the statements (i.e., they were more averse; p(F) &lt; 0.05) tended to (i) consume less of all beverage types, (ii) consume a higher proportion of white wine (p(r) &lt; 0.05), and (iii) were more likely to be female or PROP super-tasters. The results suggest that self-reported aversion to specific sensory attributes is associated with not only lower overall intake of alcoholic beverages, but also a shift in the relative proportions of beverage type consumed; a key finding for studies investigating how taste perception impacts alcohol consumption.

Association of food insecurity with dietary patterns and expenditure on food, alcohol and tobacco amongst indigenous Inuit in Greenland: results from a population health survey

BackgroundAmongst the indigenous Greenlandic Inuit, the experience of food insecurity has been attributed to a lack of money to buy enough food of sufficient quality to sustain a family, although a preference for alcohol and tobacco over food has also been cited. The purpose of the article was to compare dietary patterns and expenditure on food, alcoholic beverages and tobacco between survey participants who reported food insecurity and those who did not.MethodsA countrywide cross-sectional health survey was carried out among 1886 adult Greenlandic Inuit in 2018. Diet was estimated by a food frequency questionnaire. Food insecurity status was based on the household hunger scale. Analyses were carried out by univariate general linear models adjusted for age, sex and social position.ResultsNine percent of the participants reported food insecurity. Food insecurity was higher among younger participants, men and participants with low social position. Food insecure participants more often chose an unhealthy dietary pattern (43% vs. 32%) and they reported a higher energy intake. The food insecure spent the same amount of money on food as other participants but less on nutritious food and more on non-nutritious food. The cost per kilojoule (kJ) of the food of the food insecure was lower than that of the food secure (DKK 8.0 and 9.0 per 1000 kJ, respectively). The food insecure participants also spent considerably more on alcohol and tobacco.ConclusionsThe results suggest that it is not only unemployment and lack of money that creates food insecurity and unhealthy dietary patterns in Greenland. Food insecure participants gave higher priority to buying non-nutritious food, alcohol and tobacco than did food secure participants. There seems to be at least two population subgroups in Greenland with poverty and substance use, respectively, as the immediate determinants for food insecurity. The results are important for the design of interventions against food insecurity and unhealthy dietary patterns.

LRRK2 Gene Variants Associated With a Higher Risk for Alcohol Dependence in Multiethnic Populations.

Background: Genetics influence the vulnerability to alcohol use disorders, and among the implicated genes, three previous studies have provided evidences for the involvement of LRRK2 in alcohol dependence (AD). LRRK2 expression is broadly dysregulated in postmortem brain from AD humans, as well as in the brain of mice with alcohol dependent-like behaviors and in a zebrafish model of alcohol preference. The aim of the present study was to evaluate the association of variants in the LRRK2 gene with AD in multiethnic populations from South and North America.Methods: Alcohol-screening questionnaires [such as CAGE and Alcohol Use Disorders Identification Test (AUDIT)] were used to determine individual risk of AD. Multivariate logistic regression analyses were done in three independent populations (898 individuals from Bambuí, Brazil; 3,015 individuals from Pelotas, Brazil; and 1,316 from the United States). Linkage disequilibrium and conditional analyses, as well as in silico functional analyses, were also conducted.Results: Four LRRK2 variants were significantly associated with AD in our discovery cohort (Bambuí): rs4768231, rs4767971, rs7307310, and rs1465527. Two of these variants (rs4768231 and rs4767971) were replicated in both Pelotas and US cohorts. The consistent association signal (at the LRRK2 locus) found in populations with different genetic backgrounds reinforces the relevance of our findings.Conclusion: Taken together, these results support the notion that genetic variants in the LRRK2 locus are risk factors for AD in humans.