Promote Alcohol Consumption Research Articles

Public Perception on the Effect of Alcohol Consumption Among Commercial Drivers in Nsukka Urban, Enugu State

This study examined public perception on the effect of alcohol consumption among commercial drivers in Nsukka Urban, Enugu State. Using a sound methodology, numerous findings were made. The socio-demographics of the respondents indicated that both sexes were well represented in the study (male, 45.6% and female, 54.4%). Majority of the respondents (51.1%) were between the ages of 18-27, and majority were also single (76.7%). Data also indicated that majority of the respondents (71.7%) had tertiary education and 56.7% are students. Lastly, all the respondents were Christians. On the substantive issues of the study, the study revealed that the rate of alcohol consumption among commercial drivers in Nsukka Urban is high. It was also found that commercial drivers take alcohol on the wrong notion that makes them energetic and increases their level of concentration while driving. It was observed that even new drivers are socialized into this notion, such that alcohol consumption has become a convention among commercial drivers. The study equally found that poor awareness on the consequences of drunk driving, and easy accessibility to alcoholic drinks are the other factors that promote alcohol consumption among commercial drivers. It was equally reveled in this study that alcohol consumption by commercial drivers reduces driving skills, causes accidents by making drivers to sleep while driving or loose concentration, and had health effects on the drivers.

The impact of alcohol consumption on economic growth in Thailand

The nighttime economy has always been an important part of tourism in Thailand. The alcohol industry contends that lifting alcohol restrictions will promote tourism and, consequently, generate additional income. Endogenous Growth Theory, however, emphasizes on investing in human capital, innovation, and knowledge as the most important factors that affect economic growth for a nation. Alcohol consumption incurs opportunity costs, as households lose financial resources and time that could be invested in children’s development. Relaxing control measures to promote alcohol consumption should impede economic development by diminishing the quality of human resources. The paper, therefore, aims to estimate the impact of alcohol consumption on economic growth by using 1990–2019 annual data from Thailand. By adopting Autoregressive Distributed Lag (ARDL) approach, the results reveal that alcohol consumption has significant and negative effects on economic growth in the long run. The statistic tests demonstrate no presence of serial correlation, heteroskedasticity, as well as, endogeneity problems. The finding has been corroborated in international studies, in which alcohol consumption contributes to substantial social and economic costs of the society.

Traumatic Brain Injury Exacerbates Alcohol Consumption and Neuroinflammation with Decline in Cognition and Cholinergic Activity.

Traumatic brain injury (TBI) is a global health challenge, responsible for 30% of injury-related deaths and significantly contributing to disability. Annually, over 50 million TBIs occur worldwide, with most adult patients at emergency departments showing alcohol in their system. TBI is also a known risk factor for alcohol abuse, yet its interaction with alcohol consumption remains poorly understood. In this study, we demonstrate that the fluid percussion injury (FPI) model of TBI in mice significantly increases alcohol consumption and impairs cognitive function. At cellular levels, FPI markedly reduced the number and activity of striatal cholinergic interneurons (CINs) while increasing microglial cells. Notably, depleting microglial cells provided neuroprotection, mitigating cholinergic loss and enhancing cholinergic activity. These findings suggest that TBI may promote alcohol consumption and impair cognitive abilities through microglia activation and consequently reduced cholinergic function. Our research provides critical insights into the mechanisms linking TBI with increased alcohol use and cognitive deficits, potentially guiding future therapeutic strategies.

Role of Chemokine Cxcl12a in Mediating the Stimulatory Effects of Ethanol on Embryonic Development of Subpopulations of Hypocretin/Orexin Neurons and Their Projections.

Studies in zebrafish and rats show that embryonic ethanol exposure at low-moderate concentrations stimulates hypothalamic neurons expressing hypocretin/orexin (Hcrt) that promote alcohol consumption, effects possibly involving the chemokine Cxcl12 and its receptor Cxcr4. Our recent studies in zebrafish of Hcrt neurons in the anterior hypothalamus (AH) demonstrate that ethanol exposure has anatomically specific effects on Hcrt subpopulations, increasing their number in the anterior AH (aAH) but not posterior AH (pAH), and causes the most anterior aAH neurons to become ectopically expressed further anterior in the preoptic area (POA). Using tools of genetic overexpression and knockdown, our goal here was to determine whether Cxcl12a has an important function in mediating the specific effects of ethanol on these Hcrt subpopulations and their projections. The results demonstrate that the overexpression of Cxcl12a has stimulatory effects similar to ethanol on the number of aAH and ectopic POA Hcrt neurons and the long anterior projections from ectopic POA neurons and posterior projections from pAH neurons. They also demonstrate that knockdown of Cxcl12a blocks these effects of ethanol on the Hcrt subpopulations and projections, providing evidence supporting a direct role of this specific chemokine in mediating ethanol's stimulatory effects on embryonic development of the Hcrt system.

Embryonic ethanol exposure induces ectopic Hcrt and MCH neurons outside hypothalamus in rats and zebrafish: Role in ethanol-induced behavioural disturbances.

Embryonic exposure to ethanol increases the risk for alcohol use disorder in humans and stimulates alcohol-related behaviours in different animal models. Evidence in rats and zebrafish suggests that this phenomenon induced by ethanol at low-moderate concentrations involves a stimulatory effect on neurogenesis and density of hypothalamic neurons expressing the peptides, hypocretin/orexin (Hcrt) and melanin-concentrating hormone (MCH), known to promote alcohol consumption. Building on our report in zebrafish showing that ethanol induces ectopic expression of Hcrt neurons outside the hypothalamus, we investigated here whether embryonic ethanol exposure also induces ectopic peptide neurons in rats similar to zebrafish and affects their morphological characteristics and if these ectopic neurons are functional and have a role in the ethanol-induced disturbances in behaviour. We demonstrate in rats that ethanol at a low-moderate dose, in addition to increasing Hcrt and MCH neurons in the lateral hypothalamus where they are normally concentrated, induces ectopic expression of these peptide neurons further anterior in the nucleus accumbens core and ventromedial caudate putamen where they have not been previously observed and causes morphological changes relative to normally located hypothalamic neurons. Similar to rats, embryonic ethanol exposure at a low-moderate dose in zebrafish induces ectopic Hcrt neurons anterior to the hypothalamus and alters their morphology. Notably, laser ablation of these ectopic Hcrt neurons blocks the behavioural effects induced by ethanol exposure, including increased anxiety and locomotor activity. These findings suggest that the ectopic peptide neurons are functional and contribute to the ethanol-induced behavioural disturbances related to the overconsumption of alcohol.

Permission to Rebel: A Critical Evaluation of Alcohol Consumption and Party Tourism

There is increasing societal worry about the long and short-term medical implications of binge drinking. There is also societal and fiscal concern about the impact that the rowdy carnivalesque behaviours engendered by the heavy drinking expected during a party tourism holiday has upon both the tourist and the local community. Therefore, a multi-disciplinary analysis of extant literature relating to the party tourism phenomenon and the consumption of excess alcohol which identifies gaps in current knowledge is timely. Reviewed from a British tourist perspective, the party tourism enclave primarily hosts friendship and rites of passage groups, and stag and hen parties where a high alcohol consumption is an expected, if not compulsory, holiday behaviour. The authors go beyond sole recognition of excessive alcohol consumption in beach destinations using thematic analysis to assess the role of the communal enclave space, the power of place and representations of drinking to excess via media and holiday discourses. This is measured in the context of culturally (un)acceptable behaviours within different drinking groups according to demographics, peer group pressures, purpose of holiday and personal incentive to drink. This links to roles of social media, levels of risk tourists are willing to take, memories of holiday drinking experiences, the role the hospitality and tourism industry in promoting alcohol consumption and levels of governance and policing within the party tourism destination. Recommendations are made for future empirical research to inform policy and practice within party and nightlife destinations.

Intended or unintended adverse effects? The impact of ambiguous "Drink Responsibly" alcohol campaign messages on the drinking intentions of college students

Although alcohol companies promote “responsible drinking” health campaign messages voluntarily, critics are skeptical of the industry’s campaign, especially given that its messages are too ambiguous to be effective. This study examined how strategically ambiguous messages, in comparison to informative messages, impact college students’ perception of their knowledge as well as the psychological reactance tendency and subsequently influence the formation of attitudes and intent toward responsible drinking practices and alcohol consumption. How alcohol involvement level interacts with the type of message was also examined. An online experiment revealed that strategically ambiguous messages by alcohol companies may serve to solidify their consumer bases by promoting alcohol consumption among college students. When exposed to ambiguous messages, heavier drinkers reported their perceived knowledge level as significantly higher. The false or naïve perception of knowledge induced by ambiguous messages influenced college students’ formation of more positive attitudes toward drinking and consequently engendered greater intent to drink. While informative messages led to more psychological reactance – especially among heavier drinkers – such aroused reactance did not lead to more favorable attitudes toward drinking or intent to drink, meaning there was no boomerang effect of psychological reactance induced by informative messages. The study concludes that the industry’s alcohol responsibility message carries an “adverse effect” from a public health standpoint.

Dose-dependent induction of CPP or CPA by intra-pVTA ethanol: Role of mu opioid receptors and effects on NMDA receptors

The neurobiological mechanisms underlying alcohol motivational properties are still not fully understood, however, the mu-opioid receptors (MORs) have been evidenced as central elements in the manifestation of the alcohol reinforcing properties. Drug-associated environmental stimuli can trigger alcohol relapse and promote alcohol consumption whereby N-methyl-d-aspartate (NMDA) receptors play a pivotal role. Here we sought to demonstrate, for the first time, that ethanol induces conditioned place preference or aversion (CPP or CPA) when administered locally into the ventral tegmental area (VTA) and the associated role of MORs. We further analyzed the changes in the expression and mRNA levels of GluN1 and GluN2A subunits in designated brain areas. The expression of CPP or CPA was characterized following intra-VTA ethanol administration and we showed that either reinforcing (CPP) or aversive (CPA) properties are dependent on the dose administered (ranging here from 35 to 300 nmol). Furthermore, the critical contribution of local MORs in the acquisition of CPP was revealed by a selective antagonist, namely β-Funaltrexamine. Finally, modifications of the expression of NMDA receptor subunits in the Nucleus Accumbens (NAc) and Hippocampus after ethanol-induced CPP were analyzed at the proteomic and transcriptomic levels by western blot and In Situ Hybridation RNAscope techniques, respectively. Results showed that the mRNA levels of GluN2A but not GluN1 in NAc are higher after ethanol CPP. These novel results pave the way for further characterisation of the mechanisms by which ethanol motivational properties are associated with learned environmental cues.

Alcohol consumption and self-rated health among older people: population-based study in Sweden.

To analyse alcohol consumption and its association with self-rated health among a representative sample of older people in mid-Sweden. Over the past decades, alcohol consumption has increased in the older population in Sweden, but few studies have investigated the association between alcohol consumption and self-rated health in this group. The aim was therefore to investigate alcohol consumption and self-rated health among older Swedes. The study is based on a cross-sectional study of 11,716 men and women, 65 years and over, answering a survey questionnaire sent to a random population sample in mid-Sweden in 2012. We assessed alcohol consumption with AUDIT-C and its association with self-rated health using logistic regression analysis, adjusting for age, economic situation, educational level, BMI, physical activity, social support and medication use. Men (83%) were more prone to drink alcohol compared to women (71%). The prevalence of risk drinking was about 2% for both genders. Alcohol consumption declined with age. Moderate consumption of alcohol was associated with lower probability of poor self-rated health compared to non-drinking with an adjusted odds ratio 0.64 (95% confidence interval: 0.54-0.76) for men and 0.68 (0.59-0.79) for women. Since the study was cross-sectional the direction of the association could not be determined, and the results should not be interpreted as an argument for promoting alcohol consumption among older people.

Consequences of alcohol use, and its association with psychological distress, sensitivity to emotional contagion and age of onset of alcohol use, in Uruguayan youth with or without college degree.

Psychological distress can promote alcohol consumption during emerging adulthood. Still unknown is, however, how predisposition to emotional contagion alters psychological distress, and how these phenomena are affected by level of education. The present study analyzed the effect of psychological distress, age of first contact with alcohol (early, late), and predisposition to emotional contagion on alcohol-induced negative consequences and on the volume of alcohol consumed during the last year. We also described alcohol-use behaviors as a function of sex, maximum level of education and age of first contact with alcohol, in 1505 youth from Uruguay (18-30 years). A survey measured alcohol use (Alcohol Use Disorders Identification Test and ad-hoc questionnaire), negative consequences of alcohol use [young adult alcohol consequences questionnaire (YAACQ)], psychological distress (Kessler scale) and proclivity to emotional contagion (Doherty Emotional contagion scale). The patterns of alcohol use were greater in men vs. women and in those featuring an early age of first alcohol use, yet similar in college and non-college graduates. Early drinkers had greater levels of psychological distress than late-onset drinkers. There was a significant bivariate and multiple correlation between psychological distress and the number of negative consequences of alcohol experienced during the last year, which remained significant even after controlling for total volume of alcohol consumed. Significant associations emerged between YAACQ scores and frequency of heavy episodic or binge drinking, and between psychological distress and emotional contagion, but not between emotional contagion and any of the remaining variables. Psychological distress was not significantly correlated with heavy episodic or binge drinking. The study indicates that, during adolescence and youth, psychological distress is associated with experiencing negative consequences of alcohol consumption. The study also suggested that greater levels of psychological distress may underlie the facilitating effect of an early age of drinking onset upon alcohol drinking patterns.

Inhibition of FGF Receptor-1 Suppresses Alcohol Consumption: Role of PI3 Kinase Signaling in Dorsomedial Striatum.

Excessive alcohol intake leads to mesostriatal neuroadaptations, and to addiction phenotypes. We recently found in rodents that alcohol increases fibroblast growth factor 2 (FGF2) expression in the dorsomedial striatum (DMS), which promotes alcohol consumption. Here, we show that systemic or intra-DMS blockade of the FGF2 receptor, FGF receptor-1 (FGFR1), suppresses alcohol consumption, and that the effects of FGF2-FGFR1 on alcohol drinking are mediated via the phosphoinositide 3 kinase (PI3K) signaling pathway. Specifically, we found that sub-chronic alcohol treatment (7 d × 2.5 g/kg, i.p.) increased Fgfr1 mRNA expression in the dorsal hippocampus and dorsal striatum. However, prolonged and excessive voluntary alcohol consumption in a two-bottle choice procedure increased Fgfr1 expression selectively in DMS. Importantly, systemic administration of the FGFR1 inhibitor PD173074 to mice, as well as its infusion into the DMS of rats, decreased alcohol consumption and preference, with no effects on natural reward consumption. Finally, inhibition of the PI3K, but not of the mitogen-activated protein kinase (MAPK) signaling pathway, blocked the effects of FGF2 on alcohol intake and preference. Our results suggest that activation of FGFR1 by FGF2 in the DMS leads to activation of the PI3K signaling pathway, which promotes excessive alcohol consumption, and that inhibition of FGFR1 may provide a novel therapeutic target for alcohol use disorder.SIGNIFICANCE STATEMENT Long-term alcohol consumption causes neuroadaptations in the mesostriatal reward system, leading to addiction-related behaviors. We recently showed that alcohol upregulates the expression of fibroblast growth factor 2 (FGF2) in dorsomedial striatum (DMS) or rats and mice, and in turn, FGF2 increases alcohol consumption. Here, we show that long-term alcohol intake also increases the expression of the FGF2 receptor, FGFR1 in the DMS. Importantly, inhibition of FGFR1 activity by a selective receptor antagonist reduces alcohol drinking, when given systemically or directly into the DMS. We further show that the effects of FGF2-FGFR1 on alcohol drinking are mediated via activation of the PI3K intracellular signaling pathway, providing an insight on the mechanism for this effect.

Role Reversal: The Influence of Slot Machine Gambling on Subsequent Alcohol Consumption.

Experimental studies examining the relationship between alcohol use and gambling have focused predominantly on alcohol's influence on gambling behavior. There has been little consideration of the reverse pathway: whether gambling influences subsequent alcohol use. Two experiments examined whether gambling and gambling outcomes (i.e. profits during a gambling session) influenced subsequent alcohol consumption. Experiment 1 (n = 53) used an ad libitum consumption test, in which participants could request beverages during a 30min window. Experiment 2 (n = 29) used a beer taste test procedure, in which participants were asked to rate a series of beers. In both studies, male regular gamblers were assigned to watch a television show or play a modern slot machine for 30min, before being provided with access to alcohol. On the ad libitum procedure, gambling significantly increased the number of alcoholic drinks ordered, the volume of alcohol consumed, the participants' speed of drinking, and their intention to drink alcohol. These effects were not corroborated using the taste test procedure. Across both studies, gambling outcomes were not associated with alcohol consumption. In conjunction with prior findings, the observation that gambling can promote alcohol consumption under certain conditions highlights a possible feedback loop whereby gambling and alcohol reinforce one another. However, the divergent results between the ad libitum and taste test experiments point to boundary conditions for the effect and raise methodological considerations for future work measuring alcohol consumption in gambling environments.

Fibroblast Growth Factor 2 in the Dorsomedial Striatum Is a Novel Positive Regulator of Alcohol Consumption.

Repeated alcohol intake leads to mesostriatal neuroadaptations, resulting in drinking escalation and addiction phenotypes. Fibroblast growth factor 2 (FGF2) has been shown to interact with the mesostriatal dopaminergic system, and has been implicated in the actions of psychostimulants in the brain, and in several psychiatric disorders. Here, we report on a positive regulatory feedback loop of alcohol and FGF2 in rodent models. Specifically, we found that acute alcohol exposure (2.5 g/kg, i.p.) increased the mRNA expression of Fgf2 in the dorsal hippocampus, nucleus accumbens, and dorsal striatum. Longer alcohol exposure (7 d × 2.5 g/kg, i.p.) restricted these increases to the dorsal striatum, and the latter effect was blocked by the dopamine D2-like receptor antagonist haloperidol. Voluntary prolonged and excessive alcohol consumption in a 2-bottle choice procedure increased Fgf2 expression selectively in dorsomedial striatum (DMS) of both mice and rats. Importantly, we found that systemic administration of recombinant FGF2 (rFGF2) in mice, or rFGF2 infusion into the dorsal striatum or DMS of rats, increased alcohol consumption and preference, with no similar effects on saccharin or sucrose consumption. Finally, we found that inhibition of the endogenous FGF2 function in the DMS, by an anti-FGF2 neutralizing antibody, suppressed alcohol consumption and preference. Together, our results suggest that alcohol consumption increases the expression of Fgf2 in the DMS, and that striatal FGF2 promotes alcohol consumption, suggesting that FGF2 in the DMS is a positive regulator of alcohol drinking.SIGNIFICANCE STATEMENT Long-term alcohol intake may lead to neuroadaptations in the mesostriatal reward system, resulting in addiction phenotypes. Fibroblast growth factor 2 (FGF2) is crucial for the development and maintenance of the mesostriatal dopaminergic system. Here, we provide evidence for the involvement of FGF2 in alcohol-drinking behaviors. We show that alcohol increases Fgf2 expression in the dorsal striatum, an effect mediated via dopamine D2-like receptors. Importantly, we show that infusion of recombinant FGF2 into the dorsomedial striatum increases alcohol consumption, whereas inhibiting the endogenous FGF2 function suppresses consumption. Thus, FGF2 is an alcohol-responsive gene constituting a positive regulatory feedback loop with alcohol. This loop leads to facilitation of alcohol consumption, marking FGF2 as a potential new therapeutic target for alcohol addiction.

Nucleus Accumbens Shell and mPFC but Not Insula Orexin-1 Receptors Promote Excessive Alcohol Drinking.

Addiction to alcohol remains a major social and economic problem, in part because of the high motivation for alcohol that humans exhibit and the hazardous binge intake this promotes. Orexin-1-type receptors (OX1Rs) promote reward intake under conditions of strong drives for reward, including excessive alcohol intake. While systemic modulation of OX1Rs can alter alcohol drinking, the brain regions that mediate this OX1R enhancement of excessive drinking remain unknown. Given the importance of the nucleus accumbens (NAc) and anterior insular cortex (aINS) in driving many addictive behaviors, including OX1Rs within these regions, we examined the importance of OX1Rs in these regions on excessive alcohol drinking in C57BL/6 mice during limited-access alcohol drinking in the dark cycle. Inhibition of OX1Rs with the widely used SB-334867 within the medial NAc Shell (mNAsh) significantly reduced drinking of alcohol, with no effect on saccharin intake, and no effect on alcohol consumption when infused above the mNAsh. In contrast, intra-mNAsh infusion of the orexin-2 receptor TCS-OX2-29 had no impact on alcohol drinking. In addition, OX1R inhibition within the aINS had no effect on excessive drinking, which was surprising given the importance of aINS-NAc circuits in promoting alcohol consumption and the role for aINS OX1Rs in driving nicotine intake. However, OX1R inhibition within the mPFC did reduce alcohol drinking, indicating cortical OXR involvement in promoting intake. Also, in support of the critical role for mNAsh OX1Rs, SB within the mNAsh also significantly reduced operant alcohol self-administration in rats. Finally, orexin ex vivo enhanced firing in mNAsh neurons from alcohol-drinking mice, with no effect on evoked EPSCs or input resistance; a similar orexin increase in firing without a change in input resistance was observed in alcohol-naïve mice. Taken together, our results suggest that OX1Rs within the mNAsh and mPFC, but not the aINS, play a central role in driving excessive alcohol drinking.

Mu-opioid receptor activation in the medial shell of nucleus accumbens promotes alcohol consumption, self-administration and cue-induced reinstatement

Endogenous opioid signaling in ventral cortico-striatal-pallidal circuitry is implicated in elevated alcohol consumption and relapse to alcohol seeking. Mu-opioid receptor activation in the medial shell of the nucleus accumbens (NAc), a region implicated in multiple aspects of reward processing, elevates alcohol consumption while NAc opioid antagonists reduce it. However, the precise nature of the increases in alcohol consumption, and the effects of mu-opioid agonists on alcohol seeking and relapse are not clear. Here, we tested the effects of the mu-opioid agonist [D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO) in rat NAc shell on lick microstructure in a free-drinking test, alcohol seeking during operant self-administration, extinction learning and expression, and cue-reinforced reinstatement of alcohol seeking. DAMGO enhanced the number, but not the size of drinking bouts. DAMGO also enhanced operant alcohol self-administration and cue-induced reinstatement, but did not affect extinction learning or elicit reinstatement in the absence of cues. Our results suggest that mu-opioid agonism in NAc shell elevates alcohol consumption, seeking and conditioned reinforcement primarily by enhancing the incentive motivational properties of alcohol and alcohol-paired cues, rather than by modulating palatability, satiety, or reinforcement.

A family history of Type 1 alcoholism differentiates alcohol consumption in high cortisol responders to stress

BackgroundThe differentiation between high and low cortisol responders to stress is of interest in determining the risk factors which may, along with genetic vulnerability, influence alcohol intake. Study 1: MethodsThirty-two healthy volunteers, family history positive to alcoholism (FHP, n=16) and family history negative (FHN, n=16) attended two laboratory sessions during which alcohol or placebo was offered. ResultsThere were no differences in consumption of alcohol or placebo between FHP and FHN subjects. Study 2: MethodsFifty-eight healthy social drinkers, FHP (n=27) and FHN (n=31) attended two laboratory sessions. They were administered either alcohol or placebo in both sessions they attended. All subjects underwent either a stress task (the Trier Social Stress Test, TSST) or a stress-free period, at two separate occasions, before being offered beverage. After the salivary cortisol analysis, subjects in each group were divided into high (HCR) or low (LCR) cortisol responders. ResultsAfter stress, subjects who were FHP-HCR consumed more alcohol than FHN-HCR. There were no differences in the placebo intake between FHP and FHN subjects regardless of their cortisol response. ConclusionsThis result indicates that stress promotes alcohol consumption only in subjects with a family history of Type 1 alcoholism who show an increase in cortisol response to stress. This behaviour is similar to that previously observed in alcohol dependent individuals after stress and thus could represent an endophenotype posing a risk for future development of alcohol use disorders.

Salsolinol, free of isosalsolinol, exerts ethanol-like motivational/sensitization effects leading to increases in ethanol intake

Salsolinol is formed non-enzymatically when ethanol-derived acetaldehyde binds to dopamine, yielding 2 distinct products, i.e., salsolinol and isosalsolinol. Early animal studies, revealing that salsolinol promotes alcohol consumption and recent evidence that animals will readily self-administer salsolinol into the posterior ventral tegmental area (p-VTA) together with the finding that salsolinol is able to induce conditioned place preference and to increase locomotor activity, have outlined a role of salsolinol in the behavioral and neurobiological actions of ethanol. Until recently, the only commercially available salsolinol was a mixture containing 85% salsolinol and 10–15% isosalsolinol. The possibility thus exists that either salsolinol or isosalsolinol explains the reinforcing properties of ethanol. We report here that a newly available salsolinol is free of isosalsolinol. Thus, salsolinol, free of isosalsolinol, was injected intracerebrally (30 pmol/0.2 μL, into the ventral tegmental area [VTA]) or intraperitoneally (i.p.) (10 mg/kg) to naïve rats bred as alcohol drinkers to study salsolinol's motivational effects and its role on voluntary ethanol intake. Salsolinol produced conditioned place preference and increased locomotor activity, whether injected intra-VTA or intraperitoneally. Following systemic (i.p.) administration of 10 mg/kg salsolinol, this molecule was detected in vivo by microdialysis of neostriatum, reaching an estimated concentration of 100 nM in the dialyzate. These results indicate that systemically administered salsolinol is able to cross the blood–brain barrier (BBB). Repeated administration of salsolinol sensitized rats to the locomotor activity and led to increases in voluntary ethanol consumption, which was prevented by intra-VTA pretreatment with naltrexone.

Ethanol Induces Conditioned Social Preference in Male Mice

Affiliative social interactions promote alcohol consumption, and alcohol also promotes affiliative behavior. Furthermore, for most species, moderate doses of ethanol (EtOH) and social affiliation are each rewarding. However, animal studies of drug and EtOH reward typically test individuals in isolation. To address social dimensions of EtOH reward, this study tested EtOH-induced conditioned social preference in male C57BL/6 mice with (ORCHX+T) and without (ORCHX) testosterone. ORCHX+T males received EtOH (0, 1, 2, or 3 g/kg) intraperitoneally and were paired 4× for 30 minutes each with 1 of 2 stimulus males: with the CS- stimulus male after saline injection and with the CS+ male following EtOH. After pairing, time spent with CS+ and CS- males was measured in a 10-minute test. ORCHX+T test males showed conditioned preference for the CS+ male in response to 3 g/kg EtOH (change in preference: +71.3 ± 30.0 s/10 min, p < 0.05), but not for 0, 1, or 2 g/kg. By contrast, ORCHX males did not demonstrate conditioned preference for 3 g/kg EtOH (+16.0 ± 24.3 s/10 min, p > 0.05). In separate groups of mice, stimulus males (IS+) received EtOH during pairing to determine whether test mice prefer another intoxicated mouse. Both ORCHX+T and ORCHX test mice showed an increase in preference score for the IS+ mouse (ORCHX+T: +68.1 ± 24.0 seconds; ORCHX: +58.9 ± 19.6 seconds, p < 0.05). These data demonstrate that EtOH promotes social preference in male mice, as it does in females. Testosterone enhances this effect.

Alcohol drinking patterns and biomarkers of coronary risk in the Spanish population

Background and aimsTo estimate the association between patterns of alcohol consumption and biomarkers of coronary heart disease (CHD) risk. Methods and resultsCross-sectional study among 10,793 individuals representative of the Spanish population aged ≥18 years. The threshold between moderate and heavy drinking was 40 g of alcohol/day in men and 24 g/day in women. Binge drinking was defined as intake of ≥80 g of alcohol in men and ≥60 g in women at any drinking occasion in the preceding 30 days. Analyses were performed with generalized linear models with adjustment for the main confounders, and results were expressed as the percentage change in the geometric mean (PCGM). Compared to non-drinkers, moderate and heavy drinkers had progressively higher serum HDL-cholesterol, with a PCGM ranging from 4.8% (95% CI: 3.7–6.0%) in moderate drinkers without binge drinking (MNB) to 9.6% (5.1–14.2%) in heavy drinkers with binge drinking (HB). Fibrinogen decreased progressively with alcohol intake, from −2.2% (−3.1 to −1.3%) in MNB to −5.8% (−9.4 to −2.0%) in HB. Leptin, glycated hemoglobin and the HOMA-index also decreased with increasing alcohol intake, and particularly with binge drinking. ConclusionsModerate alcohol intake is associated with improved HDL-cholesterol, fibrinogen and markers of glucose metabolism, which is consistent with the reduced CHD risk of moderate drinkers in many studies. Heavy and binge drinking were also associated with favorable levels of CHD biomarkers; since these drinking patterns produce substantial health harms, our results should not be used to promote alcohol consumption.

Galanin-3 Receptor Antagonism by SNAP 37889 Reduces Motivation to Self-administer Alcohol and Attenuates Cue-Induced Reinstatement of Alcohol-Seeking in iP Rats

The neuropeptide galanin has a role in promoting alcohol consumption and general feeding behavior. The galanin-3 receptor (GALR3) subtype is implicated in modulating the consumption of alcohol and has therefore been identified as a potential target for new pharmacotherapies to treat alcohol use disorders. We have previously shown that the selective GALR3 antagonist SNAP 37889 reduced voluntary alcohol consumption in iP (alcohol-preferring) rats. The present study firstly aimed to investigate the effect of GALR3 antagonism on the motivational properties of alcohol. Secondly, the potential of GALR3 as a therapeutic target in the prevention of relapse was investigated in response to alcohol-conditioned cues. Administration of SNAP 37889 (30 mg/kg, i.p.) significantly reduced the breakpoint for ethanol under a progressive-ratio operant responding schedule of reinforcement. SNAP 37889 also significantly reduced reinstatement of alcohol-seeking in response to re-exposure to conditioned cues that were previously associated with the availability of alcohol. Collectively, results from the current study provide new evidence of GALR3 involvement in cue-induced relapse and provide further evidence that GALR3 antagonism reduces the motivational drive to consume alcohol. These findings validate further research in to the potential use of SNAP 37889 and other GALR3 antagonists to treat alcohol abuse disorders in humans.