Decreased Alcohol Intake Research Articles

Deep Transcranial Magnetic Stimulation of the Dorsolateral Prefrontal Cortex in Alcohol Use Disorder Patients: Effects on Dopamine Transporter Availability and Alcohol Intake

Repetitive Transcranial Magnetic Stimulation (rTMS) of the dorsolateral prefrontal cortex may affect neuro-adaptations associated with alcohol use disorder (AUD), potentially influencing craving and alcohol intake. We investigated alcohol intake and dopamine transporter (DAT) availability by Single Photon Emission Computed Tomography (SPECT) in the striatum of AUD patients before and after deep rTMS. Fourteen patients underwent baseline clinical and SPECT assessment. Eleven out of fourteen patients were randomized into two groups for the REAL (n.5) or SHAM (n.6) treatment. Clinical and SPECT evaluations were then carried out after four weeks of rTMS sessions (T1). At baseline, AUD patients showed higher striatal DAT availability than healthy control subjects (HC). Patients receiving the REAL stimulation revealed a reduction in DAT availability at T1, whereas the SHAM-treated group did not. In addition, patients receiving the REAL stimulation had a decrease in alcohol intake. The results of this longitudinal pilot study may suggest a modulatory effect of deep rTMS on dopaminergic terminals and a potential clinical efficacy in reducing alcohol intake in AUD patients. Further investigations are required to confirm these preliminary data.

Nalmefene against alcohol use disorder: A report of one case

IntroductionAlcohol consumption represents a significant factor for mortality in the world: 6.3% in men and 1.1% in women. Alcohol use disorder is also very common: 5.4% in men and 1.5% in women. Despite its high frequency and the seriousness of this disorder, only 8% of all alcohol-dependents are ever treated. One potentially interesting treatment option is oriented toward reducing alcohol intake.AimsTo describe one case who has improved his alcohol consumption after starting treatment with nalmefene, an opioid receptor antagonist related to naltrexone.MethodsA 35-year-old male with alcohol use disorder since 2001 came to our consult in November 2015. He was in trouble with his family and he had a liver failure. We offer a new treatment option with nalmefene 18 mg to reduce alcohol consumption.ResultsBefore to start nalmefene he drank 21 drinks/week. Six-month later, he decreased alcohol intake until 5 drinks/week with better family relationship and liver function. After starting nalmefene he complained of nausea, so we recommend to take the middle of the pill for next 7 days. After this time he returned to take one pill with good tolerance and no more side effects or withdrawal syndrome.ConclusionsNalmefene appears to be effective and safe in reducing heavy drinking and in preventing alcohol withdrawal syndrome due to its opioid receptor antagonism. This case suggests nalmefene is a potential option to help patients, who do not want or cannot get the abstinence, in reducing their alcohol consumption.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Alcohol policy changes and 22-year trends in individual alcohol consumption in a Swiss adult population: a 1993–2014 cross-sectional population-based study

ObjectiveEvidence on the impact of legislative changes on individual alcohol consumption is limited. Using an observational study design, we assessed trends in individual alcohol consumption of a Swiss adult population...

A Method for Evaluating the Reinforcing Properties of Ethanol in Rats without Water Deprivation, Saccharin Fading or Extended Access Training.

Operant oral self-administration methods are commonly used to study the reinforcing properties of ethanol in animals. However, the standard methods require saccharin/sucrose fading, water deprivation and/or extended training to initiate operant responding in rats. This paper describes a novel and efficient method to quickly initiate operant responding for ethanol that is convenient for experimenters and does not require water deprivation or saccharin/sucrose fading, thus eliminating the potential confound of using sweeteners in ethanol operant self-administration studies. With this method, Wistar rats typically acquire and maintain self-administration of a 20% ethanol solution in less than two weeks of training. Furthermore, blood ethanol concentrations and rewards are positively correlated for a 30 min self-administration session. Moreover, naltrexone, an FDA-approved medication for alcohol dependence that has been shown to suppress ethanol self-administration in rodents, dose-dependently decreases alcohol intake and motivation to consume alcohol for rats self-administering 20% ethanol, thus validating the use of this new method to study the reinforcing properties of alcohol in rats.

Recruitment of a Neuronal Ensemble in the Central Nucleus of the Amygdala Is Required for Alcohol Dependence

Abstinence from alcohol is associated with the recruitment of neurons in the central nucleus of the amygdala (CeA) in nondependent rats that binge drink alcohol and in alcohol-dependent rats. However, whether the recruitment of this neuronal ensemble in the CeA is causally related to excessive alcohol drinking or if it represents a consequence of excessive drinking remains unknown. We tested the hypothesis that the recruitment of a neuronal ensemble in the CeA during abstinence is required for excessive alcohol drinking in nondependent rats that binge drink alcohol and in alcohol-dependent rats. We found that inactivation of the CeA neuronal ensemble during abstinence significantly decreased alcohol drinking in both groups. In nondependent rats, the decrease in alcohol intake was transient and returned to normal the day after the injection. In dependent rats, inactivation of the neuronal ensemble with Daun02 produced a long-term decrease in alcohol drinking. Moreover, we observed a significant reduction of somatic withdrawal signs in dependent animals that were injected with Daun02 in the CeA. These results indicate that the recruitment of a neuronal ensemble in the CeA during abstinence from alcohol is causally related to excessive alcohol drinking in alcohol-dependent rats, whereas a similar neuronal ensemble only partially contributed to alcohol-binge-like drinking in nondependent rats. These results identify a critical neurobiological mechanism that may be required for the transition to alcohol dependence, suggesting that focusing on the neuronal ensemble in the CeA may lead to a better understanding of the etiology of alcohol use disorders and improve medication development. Alcohol dependence recruits neurons in the central nucleus of the amygdala (CeA). Here, we found that inactivation of a specific dependence-induced neuronal ensemble in the CeA reversed excessive alcohol drinking and somatic signs of alcohol dependence in rats. These results identify a critical neurobiological mechanism that is required for alcohol dependence, suggesting that targeting dependence neuronal ensembles may lead to a better understanding of the etiology of alcohol use disorders, with implications for diagnosis, prevention, and treatment.

High fruit intake, lower alcohol consumption associated with lower breast cancer risk

Researchers in 2 linked studies recently published in BMJ have revealed new data on the relation of alcohol and diet with breast cancer and heart disease.1, 2 The first study found that high fruit consumption during adolescence is associated with lower breast cancer risk, whereas the second reports that increased alcohol intake in later life is associated with an increase in breast cancer. Evidence about whether fruit and vegetable intake protects against breast cancer is conflicting. Most studies in this area have assessed intake during midlife and later, which may be after the period when breast tissue is most vulnerable to carcinogenic influences. As a result, researchers examined whether fruit and vegetable consumption would affect subsequent breast cancer risk. In the first study, participants included more than 90,000 premenopausal women aged 27 to 44 years from the Nurses' Health Study II who completed a questionnaire in 1991 on diet as well as more than 44,000 who completed a questionnaire in 1998 that focused on their diet during adolescence. The investigators concluded that high fruit consumption during adolescence (2.9 vs 0.5 servings per day) was associated with an approximately 25% lower risk of premenopausal breast cancer diagnosed in middle age. The association with adolescent fruit intake was stronger for both estrogen and progesterone receptor-negative cancers than estrogen and progesterone receptor-positive cancers. Specifically, apple, banana, and grape consumption during adolescence and orange and kale consumption during early adulthood were significantly associated with a reduced breast cancer risk; however, there was no link between the intake of fruit juice in either adolescence or early adulthood and risk. In an accompanying editorial, University of Oxford researchers note that although much more evidence is needed before conclusions can be drawn about the protective associations between adolescent fruit intake and breast cancer risk, fruit and vegetable intake should continue to be encouraged at all ages because of the known beneficial health effects.3 In the second study, Danish researchers analyzed the effect of a change in alcohol intake on the risk of breast cancer and heart disease. They followed the health of nearly 22,000 postmenopausal women in Denmark and found that women who increased their alcohol intake by 2 drinks per day over 5 years had an approximately 30% increased risk of breast cancer but an approximately 20% decreased risk of coronary heart disease in comparison with women who had stable alcohol intake. Decreased alcohol intake in women during the 5-year period, however, was not significantly associated with the risk of either breast cancer or coronary heart disease. The authors note that although their findings support the theory that alcohol is associated with breast cancer and coronary heart disease risk in opposite directions, the true effect of alcohol on ischemic heart disease is not certain. They add that although low to moderate alcohol consumption may provide some benefit to the heart, this is outweighed by an increased risk of breast cancer and other morbidities. Furthermore, heart disease risk can be substantially reduced by other lifestyle changes and drugs such as statins.

Combining Varenicline (Chantix) with Naltrexone Decreases Alcohol Drinking More Effectively Than Does Either Drug Alone in a Rodent Model of Alcoholism.

This study examined whether varenicline (VAR), or naltrexone (NTX), alone or in combination, reduces alcohol drinking in alcohol-preferring (P) rats with a genetic predisposition toward high voluntary alcohol intake. Alcohol-experienced P rats that had been drinking alcohol (15% v/v) for 2h/d for 4weeks were fed either vehicle (VEH), VAR alone (0.5, 1.0, or 2.0mg/kg body weight [BW]), NTX alone (10.0, 15.0, or 20.0mg/kg BW), or VAR+NTX in 1 of 4 dose combinations (0.5 VAR+10.0 NTX, 0.5 VAR+15.0 NTX, 1.0 VAR+10.0 NTX, or 1.0 VAR+15.0 NTX) at 1hour prior to alcohol access for 10 consecutive days, and the effects on alcohol intake were assessed. When administered alone, VAR in doses of 0.5 or 1.0mg/kg BW did not alter alcohol intake but a dose of 2.0mg/kg BW decreased alcohol intake. This effect disappeared when drug treatment was terminated. NTX in doses of 10.0 and 15.0mg/kg BW did not alter alcohol intake but a dose of 20.0mg/kg BW decreased alcohol intake. Combining low doses of VAR and NTX into a single medication reduced alcohol intake as well as did high doses of each drug alone. Reduced alcohol intake occurred immediately after onset of treatment with the combined medication and continued throughout prolonged treatment. Low doses of VAR and NTX, when combined in a single medication, reduce alcohol intake in a rodent model of alcoholism. This approach has the advantage of reducing potential side effects associated with each drug. Lowering the dose of NTX and VAR in a combined treatment approach that maintains efficacy while reducing the incidence of negative side effects may increase patient compliance and improve clinical outcomes for alcoholics and heavy drinkers who want to reduce their alcohol intake.

Effects of Mindfulness Interventions on Health Outcomes in Older Lesbian/Bisexual Women

PurposeLesbian and bisexual (LB) women are at higher risk for obesity, but no reported interventions focus on older LB women who are overweight or obese. The Healthy Weight in Lesbian and Bisexual Women study funded five programs (n = 266 LB women age ≥40); two examined effects of mindfulness interventions on health outcomes. MethodsAnalysis of variance and regression measured the impact of mindfulness-based programs on health behaviors and quality of life (MCS). Outcomes were also compared between intervention sites (mindfulness vs. standard weight loss approaches). ResultsMindful Eating Questionnaire (MEQ) subscale scores improved significantly from preassessment to postassessment in mindfulness interventions. LB women who reported an increase (top tertile) in mindful eating had the most significant increase in MCS scores (35.3%) compared with those with low gains (low and medium tertile) in mindfulness (3.8%). MEQ score increase predicted 40.8% of the variance (adjusted) in MCS score, R2 = .431, F(6,145) = 18.337, p < .001. Top tertile increases in mindfulness were significantly related to increases in physical activity and some nutrition outcomes. Mindfulness intervention sites showed within-person improvements in MCS and fruit and vegetable intake, whereas standard intervention sites showed within-person decreases in alcohol intake and increases in physical activity level. ConclusionsAlthough weight loss was not a primary outcome at the mindfulness sites, small but significant weight loss and weight-to-height ratio decreases were reported at all five sites. Increases in mindfulness were associated with a number of significant self-reported health improvements, including a great increase in perceived mental health quality of life. Mindfulness may be a promising practice to address health issues in aging LB women.

P002 Is enquiry regarding alcohol consumption and alcohol reduction advice acceptable to sexual health service users? A cross-sectional study of clinic attendees

Background/introduction Problem alcohol consumption is a major health problem in the UK. Alcohol assessment and behavioural advice or “brief interventions” are effective in decreasing alcohol intake in primary and secondary care but not in sexual health clinics. Aim(s)/objectives We assessed sexual health service user views towards alcohol screening using a prospective cross-sectional survey to identify any themes, which limit acceptability of these methods. Methods Age, gender, alcohol consumption measured by AUDIT-C score, and opinion towards 10 statements on alcohol screening within a sexual health clinic were assessed. Results 462 surveys were returned. Respondents were 64% female, 36% male. Most, 53.7%, were aged ≥25 years, the highest number of responses was received from those aged 20–24 (32.2%), median age category was 25–29 years. The majority of respondents, 61.6% had hazardous alcohol consumption. Males had more positive AUDIT-C scores (indicating hazardous alcohol consumption) compared to females (75% vs 54%, p Discussion/conclusion Different strategies need to be explored within sexual health for alcohol consumption reduction interventions as clinic users are younger, have higher rates of hazardous alcohol consumption and are potentially more resistant to standard brief interventions.

Dopamine receptor agonists modulate voluntary alcohol intake independently of individual levels of alcohol intake in rats.

RationaleIndividual susceptibility to alcohol use disorder has been related to functional changes in dopaminergic neurotransmission.ObjectivesThe aim of the current work was to assess the effects of selective dopamine D1 and D2 receptor agonists and antagonists on alcohol consumption in rats that differ in individual levels of alcohol intake.MethodsThe effects of the dopamine D1 receptor agonist SKF 82958, the dopamine D1 receptor antagonist SCH 23390, the dopamine D2 receptor agonist sumanirole and the dopamine D2 receptor antagonist L741,626 on alcohol consumption and preference were assessed at different time points after treatment in subgroups of low and high alcohol drinking rats (LD and HD) using an intermittent alcohol access paradigm.ResultsSKF 82958 decreased alcohol intake and alcohol preference throughout the 24-h session. Sumanirole decreased alcohol intake during the first 2 h, but increased alcohol intake during the remainder of the session. The effects of SKF 82958 and sumanirole on alcohol intake and alcohol preference were comparable in LD and HD. By contrast, the dopamine receptor antagonists SCH 23390 and L741,626 did not alter alcohol consumption in either group at any time point.ConclusionsThese data indicate that stimulation of dopamine D1 receptors reduces alcohol intake, but that endogenous dopamine does not play a primary role in alcohol consumption. Moreover, the difference in alcohol consumption between LD and HD does not involve altered dopamine signaling.

Central administration of the anorexigenic peptide neuromedin U decreases alcohol intake and attenuates alcohol-induced reward in rodents.

By investigating the neurochemical mechanisms through which alcohol activates the brain reward systems, novel treatment strategies for alcohol use disorder (AUD), a chronic relapsing disease, can be developed. In contrast to the common view of the function of gut–brain peptides, such as neuromedin U (NMU), to regulate food intake and appetite, a novel role in reinforcement mediation has been implied. The anorexigenic effects of NMU are mediated via NMU2 receptors, preferably in the arcuate nucleus and paraventricular nucleus. The expression of NMU2 receptors is also expressed in several reward‐related areas in the brain, suggesting a role in reward regulation. The present experiments were therefore set up to investigate the effect of intracerebroventricular administration of NMU on alcohol‐mediated behaviors in rodents. We found that central administration of NMU attenuated alcohol‐induced locomotor stimulation, accumbal dopamine release and the expression of conditioned place preference in mice. In addition, NMU dose dependently decreased alcohol intake in high, but not in low, alcohol‐consuming rats. Central NMU administration did not alter the blood alcohol concentrations nor change the corticosterone levels in rodents. Given that AUD is a major health‐care challenge causing an enormous cost to society and novel treatment strategies are warranted, our data suggest that NMU analogues deserve to be evaluated as novel treatment of AUD in humans.

The relationship of alcohol use to weight loss in the context of behavioral weight loss treatment

Despite common wisdom that reducing alcohol intake will facilitate weight loss, little research has examined whether participants in behavioral weight loss treatments actually decrease their alcohol intake, or whether reduced alcohol intake relates to weight loss outcomes in this context. This study examined the relationship of alcohol use to energy intake excluding alcohol and to weight in 283 overweight and obese adults participating in a 26-session behavioral weight loss treatment. The majority of participants consumed low to moderate levels of alcohol at baseline. Participants who consumed alcohol at baseline meaningfully reduced their alcohol intake by end-of-treatment. Alcohol use did not relate to weight at baseline or end-of-treatment when controlling for relevant demographic variables, and change in alcohol use was unrelated to weight change in the overall sample during treatment. However, end-of-treatment alcohol intake did relate to end-of-treatment energy intake excluding alcohol. In addition, behavioral impulsivity and change in alcohol intake interacted to predict weight loss, such that decreases in alcohol intake were associated with greater percent weight loss at end-of-treatment for participants with higher levels of impulsivity. Alcohol consumption may lead to overeating episodes, and highly impulsive individuals may be at risk for increased energy intake during or after episodes of drinking. Therefore, the recommendation to reduce alcohol intake in the context of behavioral weight loss treatment seems warranted, particularly for individuals with high levels of impulsivity.

An effect of cabergoline on alcohol consumption and DRD2 expression in the brain of rats with chronic alcohol intoxication

Cabergoline is a high selective agonist of dopamine D2 receptors (D2R). The activation of D2R plays an important role in the regulation of dopamine transmission, the imbalance of which is thought to underlie the development of alcohol motivation. To examine this possibility, cabergoline effects on alcohol consumption and brain DRD2 expression in rats with chronic alcohol intoxication were studied. Male Wister rats were studied using the following methods: modelling of chronic alcohol intoxication, testing in «10% alcohol vs water» choice regimen, quantitative RT-PCR. Systemic administration of 0.5 mg/kg of cabergoline significantly decreases alcohol intake in alcohol-preferring rats. At the same time, cabergoline elevates the DRD2 expression in the midbrain and striatum of high-alcohol-preferring rats but not in intact (alcohol-naïve) animals. The involvement of cabergoline in the DRD2 expression may lead to the decrease in alcohol motivation. These findings indicate that cabergoline needs further investigations as a new potential medication for alcohol use disorder.

Influence of alcohol consumption on hydration status in healthy adults.

Introduction: Both osmolality and water intake are considered key biomarkers of the hydration status, which is necessary for adequate cellular homeostasis and wellbeing. However, alcohol intake has been shown to affect the hydration status due to an elevated diuresis effect. Objective: To evaluate the influence of alcohol consumption on the hydration status of healthy adults. Method: This study was performed in 123 adults (25-45 y, 69% women). Blood samples were collected to analyze osmolality levels and a 72 h-recall food questionnaire was used to assess total water intake (TWI): drinking water, liquids (soft drinks, juices, milk, beer, wine and spirits) and solid foods, along with alcohol intake (grams). Mann-Whitney U test was performed to analyze sex differences and correlations were performed by the Spearman test adjusted by sex. Results: No significant differences were found for TWI in men (2.19 L/d) and women (2.21 L/d). Men consumed insufficient TWI according to EFSA recommendations (men=2.5 L/d). Osmolality and liquids intake were significantly higher in men (P<0.05), as well as the general intake of alcoholic beverages (P<0.05). A positive correlation between osmolality and alcohol consumption was found in men (P<0.05), but not in women. Conclusion: A shift in the liquid intake pattern in men, by decreasing alcohol intake and promoting water drinking might be advisable in order to lower osmolality levels and achieve a better hydration status.

Reprint of: Locus coeruleus neuronal activity determines proclivity to consume alcohol in a selectively-bred line of rats that readily consumes alcohol.

Sprague-Dawley rats selectively-bred for susceptibility to stress in our laboratory (Susceptible, or SUS rats) voluntarily consume large amounts of alcohol, and amounts that have, as shown here, pharmacological effects, which normal rats will not do. In this paper, we explore neural events in the brain that underlie this propensity to readily consume alcohol. Activity of locus coeruleus neurons (LC), the major noradrenergic cell body concentration in the brain, influences firing of ventral tegmentum dopaminergic cell bodies of the mesocorticolimbic system (VTA-DA neurons), which mediate rewarding aspects of alcohol. We tested the hypothesis that in SUS rats alcohol potently suppresses LC activity to markedly diminish LC-mediated inhibition of VTA-DA neurons, which permits alcohol to greatly increase VTA-DA activity and rewarding aspects of alcohol. Electrophysiological single-unit recording of LC and VTA-DA activity showed that in SUS rats alcohol decreased LC burst firing much more than in normal rats and as a result markedly increased VTA-DA activity in SUS rats while having no such effect in normal rats. Consistent with this, in a behavioral test for reward using conditioned place preference (CPP), SUS rats showed alcohol, given by intraperitoneal (i.p.) injection, to be rewarding. Next, manipulation of LC activity by microinfusion of drugs into the LC region of SUS rats showed that (a) decreasing LC activity increased alcohol intake and increasing LC activity decreased alcohol intake in accord with the formulation described above, and (b) increasing LC activity blocked both the rewarding effect of alcohol in the CPP test and the usual alcohol-induced increase in VTA-DA single-unit activity seen in SUS rats. An important ancillary finding in the CPP test was that an increase in LC activity was rewarding by itself, while a decrease in LC activity was aversive; consequently, effects of LC manipulations on alcohol-related reward in the CPP test were perhaps even larger than evident in the test. Finally, when increased LC activity was associated with (i.e., conditioned to) i.p. alcohol, subsequent alcohol consumption by SUS rats was markedly reduced, indicating that SUS rats consume large amounts of alcohol because of rewarding physiological consequences requiring increased VTA-DA activity. The findings reported here are consistent with the view that the influence of alcohol on LC activity leading to changes in VTA-DA activity strongly affects alcohol-mediated reward, and may well be the basis of the proclivity of SUS rats to avidly consume alcohol.

Locus coeruleus neuronal activity determines proclivity to consume alcohol in a selectively-bred line of rats that readily consumes alcohol

Sprague–Dawley rats selectively-bred for susceptibility to stress in our laboratory (Susceptible, or SUS rats) voluntarily consume large amounts of alcohol, and amounts that have, as shown here, pharmacological effects, which normal rats will not do. In this paper, we explore neural events in the brain that underlie this propensity to readily consume alcohol. Activity of locus coeruleus neurons (LC), the major noradrenergic cell body concentration in the brain, influences firing of ventral tegmentum dopaminergic cell bodies of the mesocorticolimbic system (VTA-DA neurons), which mediate rewarding aspects of alcohol. We tested the hypothesis that in SUS rats alcohol potently suppresses LC activity to markedly diminish LC-mediated inhibition of VTA-DA neurons, which permits alcohol to greatly increase VTA-DA activity and rewarding aspects of alcohol. Electrophysiological single-unit recording of LC and VTA-DA activity showed that in SUS rats alcohol decreased LC burst firing much more than in normal rats and as a result markedly increased VTA-DA activity in SUS rats while having no such effect in normal rats. Consistent with this, in a behavioral test for reward using conditioned place preference (CPP), SUS rats showed alcohol, given by intraperitoneal (i.p.) injection, to be rewarding. Next, manipulation of LC activity by microinfusion of drugs into the LC region of SUS rats showed that (a) decreasing LC activity increased alcohol intake and increasing LC activity decreased alcohol intake in accord with the formulation described above, and (b) increasing LC activity blocked both the rewarding effect of alcohol in the CPP test and the usual alcohol-induced increase in VTA-DA single-unit activity seen in SUS rats. An important ancillary finding in the CPP test was that an increase in LC activity was rewarding by itself, while a decrease in LC activity was aversive; consequently, effects of LC manipulations on alcohol-related reward in the CPP test were perhaps even larger than evident in the test. Finally, when increased LC activity was associated with (i.e., conditioned to) i.p. alcohol, subsequent alcohol consumption by SUS rats was markedly reduced, indicating that SUS rats consume large amounts of alcohol because of rewarding physiological consequences requiring increased VTA-DA activity. The findings reported here are consistent with the view that the influence of alcohol on LC activity leading to changes in VTA-DA activity strongly affects alcohol-mediated reward, and may well be the basis of the proclivity of SUS rats to avidly consume alcohol.

The glucagon-like peptide 1 receptor agonist liraglutide attenuates the reinforcing properties of alcohol in rodents.

The incretin hormone, glucagon‐like peptide 1 (GLP‐1), regulates gastric emptying, glucose‐dependent stimulation of insulin secretion and glucagon release, and GLP‐1 analogs are therefore approved for treatment of type II diabetes. GLP‐1 receptors are expressed in reward‐related areas such as the ventral tegmental area and nucleus accumbens, and GLP‐1 was recently shown to regulate several alcohol‐mediated behaviors as well as amphetamine‐induced, cocaine‐induced and nicotine‐induced reward. The present series of experiments were undertaken to investigate the effect of the GLP‐1 receptor agonist, liraglutide, on several alcohol‐related behaviors in rats that model different aspects of alcohol use disorder in humans. Acute liraglutide treatment suppressed the well‐documented effects of alcohol on the mesolimbic dopamine system, namely alcohol‐induced accumbal dopamine release and conditioned place preference in mice. In addition, acute administration of liraglutide prevented the alcohol deprivation effect and reduced alcohol intake in outbred rats, while repeated treatment of liraglutide decreased alcohol intake in outbred rats as well as reduced operant self‐administration of alcohol in selectively bred Sardinian alcohol‐preferring rats. Collectively, these data suggest that GLP‐1 receptor agonists could be tested for treatment of alcohol dependence in humans.

Prazosin Reduces Alcohol Intake in an Animal Model of Alcohol Relapse.

Many alcoholics and heavy drinkers undergo repeated cycles of alcohol abstinence followed by relapse to alcohol drinking; a pattern that contributes to escalated alcohol intake over time. In rodents, alcohol drinking that is interspersed with periods of alcohol deprivation (imposed abstinence) increases alcohol intake during reaccess to alcohol. This is termed the "alcohol deprivation effect" or "ADE" and is a model of alcohol relapse in humans. We have previously reported that prazosin reduces alcohol drinking during both brief and prolonged treatment in rats selectively bred for alcohol preference ("P" rats). This study explores whether prazosin prevents alcohol "relapse" in P rats, as reflected by a reduced or abolished ADE. Adult male P rats were given 24-hour access to food and water and scheduled access to alcohol (15 and 30% v/v solutions presented concurrently) for 2h/d. After 5weeks, rats underwent imposed alcohol deprivation for 2weeks, followed by alcohol reaccess for 2weeks, and this pattern was repeated for a total of 3 cycles. Rats were injected with prazosin (0, 0.5, 1.0, or 2.0mg/kg body weight, intraperitoneally) once a day for the first 5days of each alcohol reaccess cycle. Alcohol intake increased on the first day of each alcohol reaccess cycle, demonstrating the formation of an ADE. The ADE was short-lived, lasting only 1day, during each of the 3 cycles. Prazosin, in all doses tested, prevented the expression of an ADE in all 3 alcohol reaccess cycles. Prazosin decreases alcohol intake in P rats even in a situation that would be expected to increase alcohol drinking, namely following periods of alcohol deprivation. This suggests that prazosin may be effective in reducing alcohol relapse that often occurs during attempts to achieve permanent alcohol abstinence in treatment-seeking alcoholics and heavy drinkers.

Longitudinal analysis of lifestyle habits in relation to body mass index, onset of overweight and obesity: results from a large population-based cohort in Sweden.

It is currently unknown whether the prevalence of obesity is increasing or has levelled off in Sweden and other Westernised countries. Given the major importance of lifestyle habits on weight status, we aimed to explore associations of longitudinal changes in lifestyle habits with changes in body mass index (BMI), and the onset of overweight and obesity. Participants (aged 18-84 years at baseline) were included from the Stockholm Public Health Cohort 2002-2010 (n=23,108). Weight status was from self-reported height and weight. Investigated lifestyle habits were leisure-time physical activity, and fruit, alcohol and smoking habits. We estimated associations of stable, improving or worsening lifestyle habits with longitudinal changes in BMI and onset of overweight or obesity between 2002 and 2010. Both men and women increased in weight during the eight years of follow-up. Incidence of obesity was lower in men who increased their leisure-time physical activity (Relative Risk [RR]=0.58, 95% confidence interval 0.42-0.81) than in inactive individuals; the same applied to women (RR=0.37, 0.25-0.54), and similar patterns were identified for overweight and BMI in both genders. Smoking cessation was associated with onset of obesity for men (RR=1.69, 1.15-2.50) and women (RR=1.99, 1.39-2.85). Stable low alcohol intake or decreasing alcohol intake and daily fruit intake was associated with less weight gain, but only in men. Improving physical activity in both men and women, and alcohol habits and fruit intake in men, prevents excess weight gain among adult people in Sweden. Such an improvement might diminish weight gain after smoking cessation.

Evaluation of guanfacine as a potential medication for alcohol use disorder in long-term drinking rats: behavioral and electrophysiological findings.

One of the main treatment challenges in alcohol use disorder (AUD) is the high rate of craving in combination with decreased cognitive functioning including impaired decision making and impulse control that often lead to relapse. Recent studies show that guanfacine, an α-2-adrenoceptor agonist and FDA-approved ADHD medication, attenuates stress-induced relapse of several drugs of abuse including alcohol. Here we evaluated guanfacine's effects on voluntary alcohol intake, the alcohol deprivation effect (ADE), alcohol seeking behavior, and cue/priming-induced reinstatement in Wistar rats that had voluntarily consumed alcohol for at least 2 months before treatment. In addition, guanfacine's ability to regulate glutamatergic neurotransmission was evaluated through electrophysiological recordings in medial prefrontal cortex (mPFC) slices prepared from long-term drinking rats (and alcohol-naive controls) that had received three daily guanfacine (0.6 mg/kg/day) or vehicle injections in vivo. Guanfacine decreased alcohol intake in high, but not low, alcohol-consuming rats and the effects were generally more long lasting than that of the AUD medication naltrexone. Repeated guanfacine treatment induced a long-lasting decrease in alcohol intake, persistent up to five drinking sessions after the last injection. In addition, guanfacine attenuated the ADE as well as alcohol seeking and cue/priming-induced reinstatement of alcohol seeking. Finally, subchronic guanfacine treatment normalized an alcohol-induced dysregulated glutamatergic neurotransmission in the mPFC. These results support previous studies showing that guanfacine has the ability to improve prefrontal connectivity through modulation of the glutamatergic system. Together with the fact that guanfacine appears to be clinically safe, these results merit evaluation of guanfacine's clinical efficacy in AUD individuals.