Rewarding Effects Of Alcohol Research Articles

Integrating alcohol response feedback in a brief intervention for young adult heavy drinkers who smoke: A pilot study

BackgroundMore effective approaches are needed to enhance drinking and other health behavior (e.g., smoking) outcomes of alcohol brief intervention (BI). Young adult heavy drinkers often engage in other health risk behaviors and show sensitivity to alcohol's stimulating and rewarding effects, which predicts future alcohol-related problems. However, standard alcohol BIs do not address these issues. The current pilot study tested the utility of including feedback on alcohol response phenotype to improve BI outcomes among young adult heavy drinkers who smoke (HDS). MethodsThirty-three young adult (M±SD age=23.8±2.1 years) HDS (8.7±4.3 binge episodes/month; 23.6±6.3 smoking days/month) were randomly assigned to standard alcohol BI (BI-S; n=11), standard alcohol BI with personalized alcohol response feedback (BI-ARF; n=10), or a health behavior attention control BI (AC; n=11). Alcohol responses (stimulation, sedation, reward, and smoking urge) for the BI-ARF were recorded during a separate alcohol challenge session (.8g/kg). Outcomes were past-month drinking and smoking behavior assessed at 1- and 6-months post-intervention. ResultsAt 6-month follow-up, the BI-ARF produced significant reductions in binge drinking, alcohol-smoking co-use, drinking quantity and frequency, and smoking frequency, but not maximum drinks per occasion, relative to baseline. Overall, the BI-ARF produced larger reductions in drinking/smoking behaviors at follow-up than did the BI-S or AC. ConclusionsIncluding personalized feedback on alcohol response phenotype may improve BI outcomes for young adult HDS. Additional research is warranted to enhance and refine this approach in a broader sample.

Extraversion and the Rewarding Effects of Alcohol in a Social Context.

The personality trait of extraversion has been linked to problematic drinking patterns. Researchers have long hypothesized that such associations are attributable to increased alcohol-reward sensitivity among extraverted individuals, and surveys suggest that individuals high in extraversion gain greater mood enhancement from alcohol than those low in extraversion. Surprisingly, however, alcohol administration studies have not found individuals high in extraversion to experience enhanced mood following alcohol consumption. Of note, prior studies have examined extraverted participants-individuals who self-identify as being highly social-consuming alcohol in isolation. In the present research, we used a group drinking paradigm to examine whether individuals high in extraversion gained greater reward from alcohol than did those low in extraversion and, further, whether a particular social mechanism (partners’ Duchenne smiling) might underlie alcohol reward sensitivity among extraverted individuals. Social drinkers (n 720) consumed a moderate dose of alcohol, placebo, or control beverage in groups of 3 over the course of 36 min. This social interaction was video-recorded, and Duchenne smiling was coded using the Facial Action Coding System. Results indicated that participants high in extraversion reported significantly more mood enhancement from alcohol than did those low in extraversion. Further, mediated moderation analyses focusing on Duchenne smiling of group members indicated that social processes fully and uniquely accounted for alcohol reward-sensitivity among individuals high in extraversion. Results provide initial experimental evidence that individuals high in extraversion experience increased mood-enhancement from alcohol and further highlight the importance of considering social processes in the etiology of alcohol use disorder.

Speech volume indexes sex differences in the social-emotional effects of alcohol.

Men and women differ dramatically in their rates of alcohol use disorder (AUD), and researchers have long been interested in identifying mechanisms underlying male vulnerability to problem drinking. Surveys suggest that social processes underlie sex differences in drinking patterns, with men reporting greater social enhancement from alcohol than women, and all-male social drinking contexts being associated with particularly high rates of hazardous drinking. But experimental evidence for sex differences in social-emotional response to alcohol has heretofore been lacking. Research using larger sample sizes, a social context, and more sensitive measures of alcohol's rewarding effects may be necessary to better understand sex differences in the etiology of AUD. This study explored the acute effects of alcohol during social exchange on speech volume--an objective measure of social-emotional experience that was reliably captured at the group level. Social drinkers (360 male; 360 female) consumed alcohol (.82 g/kg males; .74 g/kg females), placebo, or a no-alcohol control beverage in groups of 3 over 36-min. Within each of the 3 beverage conditions, equal numbers of groups consisted of all males, all females, 2 females and 1 male, and 1 female and 2 males. Speech volume was monitored continuously throughout the drink period, and group volume emerged as a robust correlate of self-report and facial indexes of social reward. Notably, alcohol-related increases in group volume were observed selectively in all-male groups but not in groups containing any females. Results point to social enhancement as a promising direction for research exploring factors underlying sex differences in problem drinking.

Adenosine 2A receptors modulate reward behaviours for methamphetamine.

Addiction to methamphetamine (METH) is a global health problem for which there are no approved pharmacotherapies. The adenosine 2A (A2 A ) receptor presents a potential therapeutic target for METH abuse due to its modulatory effects on striatal dopamine and glutamate transmission. Notably, A2 A receptor signalling has been implicated in the rewarding effects of alcohol, cocaine and opiates; yet, the role of this receptor in METH consumption and seeking is essentially unknown. Therefore, the current study used A2 A knockout (KO) mice to assess the role of A2 A in behaviours relevant to METH addiction. METH conditioned place preference was absent in A2 A KO mice compared with wild-type (WT) littermates. Repeated METH treatment produced locomotor sensitization in both genotypes; however, sensitization was attenuated in A2 A KO mice in a dose-related manner. METH intravenous self-administration was intact in A2 A KO mice over a range of doses and schedules of reinforcement. However, the motivation to self-administer was reduced in A2 A KO mice. Regression analysis further supported the observation that the motivation to self-administer METH was reduced in A2 A KO mice even when self-administration was similar to WT mice. Sucrose self-administration was also reduced in A2 A KO mice but only at higher schedules of reinforcement. Collectively, these data suggest that A2 A signalling is critically required to integrate rewarding and motivational properties of both METH and natural rewards.

Factors Affecting Ethanol-Induced Conditioned Place Preference and Locomotor Sensitization in Mice.

The rewarding effects of alcohol can lead to progressively heavier and more frequent drinking. Since studies of reward have mainly focused on responses to higher alcohol doses, the relations between reward and moderate/sustained alcohol exposure remain unknown. Our objective was to evaluate factors affecting the reward value of low alcohol doses and risk factors for increasing alcohol doses due to reward progression caused by alcohol exposure patterns. We thus performed conditioned place preference (CPP) and ethanol (EtOH)-induced locomotor sensitization tests in mice. Low-dose EtOH (0.5 or 1 g/kg twice/week)-induced CPP was stronger than that produced by saline control treatment, but the effect decreased with increasing numbers of conditioning trials. Moderate-dose/long-term EtOH exposure induced a weaker CPP than high-dose/short-term EtOH (2 g/kg twice/week) exposure with the same total EtOH dose (8 g/kg/experiment). Acamprosate calcium, an anti-relapse drug, preclusively reduced EtOH-induced CPP. EtOH induced CPP and locomotor sensitization in black but not white chamber, although the initial preference and the basal locomotion in each chamber were equal. Therefore the brightness of the chamber had an effect on EtOH-induced sensitization. Moreover, additional studies indicated that EtOH-induced locomotor sensitization also depends on the dose but not the administration interval. Paired associative learning with EtOH exposure is a potent factor influencing the level of reward produced by EtOH. Moreover, exposure to high doses of alcohol, even on an intermittent schedule, carries a higher risk of addiction than exposure to moderate doses over longer periods.

Dose specific effects of olanzapine in the treatment of alcohol dependence.

It is well established that the rewarding effects of alcohol are modulated by the mesolimbic dopaminergic system. Olanzapine, a D2 dopamine antagonist, has been shown to reduce alcohol craving and consumption. To clarify whether olanzapine has clinical utility in the treatment of alcohol dependence, a 12-week, double-blind, and randomized clinical trial was conducted. One hundred twenty-nine treatment-seeking alcohol-dependent adults were randomly assigned to 12weeks of olanzapine (5 vs. 2.5mg) or placebo. Outcomes examined were average drinks per drinking day (DDD), proportion of drinking days (PDD) to total days in treatment, alcohol craving, and impaired control over alcohol use. Mixed models were used to examine medication effects during the course of treatment on specified outcomes. All of the analyses indicated a main effect for time, such that there were reductions in alcohol use and craving and an increase in control over alcohol use across treatment conditions. Dose-response analyses indicated that, in comparison to placebo, participants in the 5mg group experienced reduced craving for alcohol and participants in the 2.5mg group decreased in PDD and increased in their control over alcohol use. Better control over alcohol use remained significant 6months post-treatment for the 2.5mg group. Subjective experiences of the medication suggest that 2.5 and 5mg were equally well tolerated. Results provide some support for the notion that dosage is an important consideration in relation to effectiveness; however, the cost-benefit balance does not support the clinical utility of olanzapine in treating alcohol dependence.

Chronic alcohol consumption leads to neurochemical changes in the nucleus accumbens that are not fully reversed by withdrawal

Neuropeptide Y (NPY)- and acetylcholine-containing interneurons of the nucleus accumbens (NAc) seem to play a major role in the rewarding effects of alcohol. This study investigated the relationship between chronic alcohol consumption and subsequent withdrawal and the expression of NPY and acetylcholine in the NAc, and the possible involvement of nerve growth factor (NGF) in mediating the effects of ethanol. Rats ingesting an aqueous ethanol solution over 6months and rats subsequently deprived from ethanol during 2months were used to estimate the total number and the somatic volume of NPY and cholinergic interneurons, and the numerical density of cholinergic varicosities in the NAc. The tissue content of choline acetyltransferase (ChAT) and catecholamines were also determined. The number of NPY interneurons increased during alcohol ingestion and returned to control values after withdrawal. Conversely, the number and the size of cholinergic interneurons, and the amount of ChAT were unchanged in ethanol-treated and withdrawn rats, but the density of cholinergic varicosities was reduced by 50% during alcohol consumption and by 64% after withdrawal. The concentrations of dopamine and norepinephrine were unchanged both during alcohol consumption and after withdrawal. The administration of NGF to withdrawn rats significantly increased the number of NPY-immunoreactive neurons, the size of cholinergic neurons and the density of cholinergic varicosities. Present data show that chronic alcohol consumption leads to long-lasting neuroadaptive changes of the cholinergic innervation of the NAc and suggest that the cholinergic system is a potential target for the development of therapeutic strategies in alcoholism and abstinence.

Roux-en-Y Gastric Bypass Increases Intravenous Ethanol Self-Administration in Dietary Obese Rats

Roux-en-Y gastric bypass surgery (RYGB) is an effective treatment for severe obesity. Clinical studies however have reported susceptibility to increased alcohol use after RYGB, and preclinical studies have shown increased alcohol intake in obese rats after RYGB. This could reflect a direct enhancement of alcohol’s rewarding effects in the brain or an indirect effect due to increased alcohol absorption after RGYB. To rule out the contribution that changes in alcohol absorption have on its rewarding effects, here we assessed the effects of RYGB on intravenously (IV) administered ethanol (1%). For this purpose, high fat (60% kcal from fat) diet-induced obese male Sprague Dawley rats were tested ∼2 months after RYGB or sham surgery (SHAM) using both fixed and progressive ratio schedules of reinforcement to evaluate if RGYB modified the reinforcing effects of IV ethanol. Compared to SHAM, RYGB rats made significantly more active spout responses to earn IV ethanol during the fixed ratio schedule, and achieved higher breakpoints during the progressive ratio schedule. Although additional studies are needed, our results provide preliminary evidence that RYGB increases the rewarding effects of alcohol independent of its effects on alcohol absorption.

Rewarding and aversive effects of ethanol in High Drinking in the Dark selectively bred mice

Both rewarding and aversive effects contribute to alcohol consumption. Animals genetically predisposed to be high drinkers show reduced sensitivity to the aversive effects of alcohol, and in some instances, increased sensitivity to alcohol's rewarding effects. The present studies tested the high drinking in the dark (HDID) selected lines, a genetic model of drinking to intoxication, to determine whether intake in these mice was genetically related to sensitivity to alcohol aversion or reward. Male HDID mice from the first and second replicate lines (HDID-1 and HDID-2, respectively) and mice from the heterogeneous progenitor control population (HS/Npt, or HS) were conditioned for a taste aversion to a salt solution using two doses of alcohol, and lithium chloride (LiCl) and saline controls. In separate experiments, male and female HDID-1, HDID-2 and HS mice were conditioned for place preference using alcohol. HDID mice were found to have an attenuated sensitivity to alcohol at a moderate (2 g/kg) dose compared to HS mice, but did not differ on conditioned taste aversion to a high (4 g/kg) dose or LiCl or saline injections. HDID and HS mice showed comparable development of alcohol-induced conditioned place preference. These results indicate that high blood alcohol levels after drinking in the HDID mice is genetically related to attenuated aversion to alcohol, while sensitivity to alcohol reward is not altered in these mice. Thus, HDID mice may find a moderate dose of alcohol to be less aversive than control mice and consequently may drink more because of this reduced aversive sensitivity.

β-Arrestin 2 knockout mice exhibit sensitized dopamine release and increased reward in response to a low dose of alcohol

The rewarding effects of alcohol have been attributed to interactions between opioid and dopaminergic system within the mesolimbic reward pathway. We have previously shown that ablation of β-arrestin 2 (Arrb2), a crucial regulator of μ-opioid receptor function, attenuates alcohol-induced hyperlocomotion and c-fos activation in the nucleus accumbens. Here, we further investigated the role of Arrb2 in modulating alcohol-induced dopamine (DA) release and conditioned place preference (CPP). We also assessed the functional importance of Arrb2 for μ-opioid receptor surface expression and signaling following an acute alcohol challenge. Alcohol-evoked (0.375, 0.75, and 1.5g/kg intraperitoneally) DA release was measured by in vivo microdialysis in the shell of nucleus accumbens. Reward was assessed by the CPP paradigm. Receptor function was assessed by μ-receptor binding and [(35)S]GTP-γ-S autoradiography. In Arrb2 knockout mice accumbal DA levels reach maximum response at a lower dose compared to wild-type (wt) animals. In line with these results, Arrb2 knockout mice display increased CPP for alcohol as compared to wt mice. Finally, Arrb2 mutant mice display increased μ-opioid receptor signaling in the ventral and dorsal striatum and amygdala in response to a low dose of alcohol, indicating impaired desensitization mechanisms in these mice. Our results show that Arrb2 modulates the response to low doses of alcohol on various levels including μ-opioid receptor signaling, DA release, and reward. They also reveal a clear dissociation between the effects of Arrb2 on psychomotor and reward behaviors.

The Teenage Brain

The high levels of alcohol consumption characteristic of adolescence may be in part biologically based, given that elevated consumption levels are evident during this developmental transition in other mammalian species as well. Studies conducted using a simple animal model of adolescence in the rat have shown adolescents to be more sensitive than adults to social facilitatory and rewarding effects of alcohol but less sensitive to numerous alcohol effects that may serve as cues to limit intake. These age-specific alcohol sensitivities appear related to differential rates of development of neural systems underlying different alcohol effects, as well as to an ontogenetic decline in rapid brain compensations to alcohol, termed acute tolerance. In contrast, these adolescent-typical sensitivities to alcohol do not appear to be notably influenced by pubertal increases in gonadal hormones. Although data are sparse, there are hints that similar alcohol sensitivities may be seen in human adolescents, with this developmentally decreased sensitivity to alcohol’s intoxicating effects possibly exacerbated by genetic vulnerabilities also characterized by an insensitivity to alcohol intoxication, thereby perhaps permitting especially high levels of alcohol consumption among vulnerable youths.

Effects of naltrexone on adolescent alcohol cue reactivity and sensitivity: an initial randomized trial

Adolescent alcohol use is associated with myriad adverse consequences and contributes to the leading causes of mortality among youth. Despite the magnitude of this public health problem, evidenced-based treatment initiatives for alcohol use disorders in youth remain inadequate. Identifying promising pharmacological approaches may improve treatment options. Naltrexone is an opiate receptor antagonist that is efficacious for reducing drinking in adults by attenuating craving and the rewarding effects of alcohol. Implications of these findings for adolescents are unclear; however, given that randomized trials of naltrexone with youth are non-existent. We conducted a randomized, double-blinded, placebo-controlled cross-over study, comparing naltrexone (50 mg/daily) and placebo in 22 adolescent problem drinkers aged 15-19 years (M = 18.36, standard deviation = 0.95; 12 women). The primary outcome measures were alcohol use, subjective responses to alcohol consumption, and alcohol-cue-elicited craving assessed in the natural environment using ecological momentary assessment methods, and craving and physiological reactivity assessed using standard alcohol cue reactivity procedures. Results showed that naltrexone reduced the likelihood of drinking and heavy drinking (P's ≤ 0.03), blunted craving in the laboratory and in the natural environment (P's ≤ 0.04), and altered subjective responses to alcohol consumption (P's ≤ 0.01). Naltrexone was generally well tolerated by participants. This study provides the first experimentally controlled evidence that naltrexone reduces drinking and craving, and alters subjective responses to alcohol in a sample of adolescent problem drinkers, and suggests larger clinical trials with long-term follow-ups are warranted.

Individual differences in elevated plus-maze exploration predicted higher ethanol consumption and preference in outbred mice

Psychiatric illnesses, such as anxiety, are highly comorbid with drug use disorders in general and alcohol abuse in particular. Unfortunately, the causal role of anxiety in ethanol addiction is still unclear. We asked the question whether high anxiety predicts predilection of mice to voluntarily consume more alcohol than water. In the current study, we used the voluntary alcohol intake in two bottle choice drinking paradigm to explore whether high anxiety predicts higher alcohol preference and intake in outbred Tuck-Ordinary “TO” mice. To this end, mice were tested for their anxiety-like behavior using the elevated plus maze, open field and the marble burying test prior to voluntary continuous access to increasing concentrations of alcohol solutions. To assess their taste discrimination, mice had access to saccharin and quinine solutions. Results showed that compared to low-anxious mice (LAM), high-anxious mice (HAM) showed greater consumption and preference for ethanol but not for saccharin and quinine suggesting alterations in the rewarding effects of alcohol. Taken together, these findings suggest a correlative link between trait anxiety and the behavioral responses to ethanol.

Gastric Bypass Increases Ethanol and Water Consumption in Diet-Induced Obese Rats

Roux-en-Y gastric bypass surgery (RYGB) is an effective treatment for morbid obesity. Increased alcohol abuse after RYGB resulted in recommendations to exclude patients with alcohol abuse histories from RYGB. The purpose of our study was to examine the effects of a RYGB on ethanol intake in diet-induced obese rats (high-fat diet). The animals underwent RYGB and were habituated along with their sham-operated obese controls and with lean rats to increasing concentrations of ethanol in a two-bottle choice paradigm. RYGB rats' daily consumption of ethanol averaged 2 g/kg at 2% habituation and 3.8 g/kg at 4% habituation, twice as much as sham-operated obese controls and 50% more than normal-diet lean controls. Obese controls drank on average 1 g/kg of ethanol (2 and 4%), significantly less (50%) than lean controls did. RYGB rats when given higher ethanol concentrations (6 and 8%) or no ethanol drank significantly more water than lean and obese controls did (66 and 100%, respectively), and their enhanced total fluid intake was associated with increased food intake, which was significantly higher than in lean (66% more calories; food + alcohol) and obese controls (44% more calories). The lower alcohol intake in the obese controls than in the lean rats suggests that obesity may interfere with alcohol's rewarding effects and RYGB may remove this protective effect. The overall enhancement of consummatory behaviors (both ethanol and water) suggests that RYGB may facilitate alcohol consumption, which in vulnerable individuals could lead to abuse and addiction.

Viral-Mediated Knockdown of mGluR7 in the Nucleus Accumbens Mediates Excessive Alcohol Drinking and Increased Ethanol-Elicited Conditioned Place Preference in Rats

Whether metabotropic glutamate 7 (mGluR7) -activation enhances or diminishes the reinforcing properties of psychostimulants remains unclear. We have previously shown that systemic mGluR7 activation reduced alcohol consumption and preference as well as locomotor-stimulating and rewarding properties of ethanol. In this study, we further examined the contribution of mGluR7 on the effect of ethanol within the nucleus accumbens (NAcc), a neural target for many drugs of abuse. Using short hairpin RNA (shRNA)-expressing lentiviral vectors (LV) to alter locally the activity of mGluR7 in male rats, we have shown that blocking mGluR7 expression increased ethanol consumption and preference in a two-bottle choice drinking paradigm with no effect either on saccharin or on quinine used for taste discrimination. In addition, mGluR7 knockdown increases preference for environments previously paired with low doses of ethanol in the conditioned place preference (CPP) test, as it shifted the dose-response curve for ethanol CPP to the left, indicating alterations in the rewarding effects of alcohol. More importantly, mGluR7 blockade in the dorsal striatum (DS) neither affected ethanol consumption nor ethanol-elicited CPP. These results show that levels of mGluR7 in the NAcc regulate responsiveness to alcohol. Taken together, these findings clearly demonstrate that mGluR7 signaling within the NAcc is a key modulator of functional responses to ethanol and offer an important target for regulating the addictive effects of alcohol.

Intracranial self-stimulation in FAST and SLOW mice: effects of alcohol and cocaine

Sensitivity to the stimulant and rewarding effects of alcohol may be genetically correlated traits that predispose individuals to develop an alcohol use disorder. This study aimed to examine the effects of alcohol and cocaine on intracranial self-stimulation (ICSS) in FAST and SLOW mice, which were selectively bred for extremes in alcohol stimulation. Male FAST and SLOW mice were conditioned to respond for reinforcement by direct electrical stimulation of the medial forebrain bundle (i.e., brain stimulation reward). ICSS responses were determined immediately before and after oral gavage with water or alcohol (0.3-2.4g/kg) or intraperitoneal injection with saline or cocaine (1.0-30.0mg/kg). In separate FAST and SLOW mice, the locomotor effects of these treatments were measured in activity chambers. Alcohol dose-dependently lowered the threshold for self-stimulation (θ (0)) and the frequency that maintained 50% of maximal responding (EF50) in FAST mice but did not significantly affect these parameters in SLOW mice. The largest effects of alcohol were after the 1.7- and 2.4-g/kg doses and were about 40% compared to water injection. Alcohol did not affect MAX response rates, but dose-dependently stimulated locomotor activity in FAST mice. Cocaine lowered thresholds equally in FAST and SLOW mice, although cocaine-stimulated locomotor activity was higher in the FAST than in the SLOW mice. Selective breeding for alcohol locomotor stimulation also renders the mice more sensitive to the effects of alcohol, but not cocaine, on ICSS.

Ethanol as a prodrug: brain metabolism of ethanol mediates its reinforcing effects.

While the molecular entity responsible for the rewarding effects of virtually all drugs of abuse is known, that for ethanol remains uncertain. Some lines of evidence suggest that the rewarding effects of alcohol are mediated not by ethanol per se but by acetaldehyde generated by catalase in the brain. However, the lack of specific inhibitors of catalase has not allowed strong conclusions to be drawn about its role on the rewarding properties of ethanol. The present studies determined the effect on voluntary alcohol consumption of two gene vectors, one designed to inhibit catalase synthesis and one designed to synthesize alcohol dehydrogenase (ADH), to respectively inhibit or increase brain acetaldehyde synthesis. The lentiviral vectors, which incorporate the genes they carry into the cell genome, were (i) one encoding a shRNA anticatalase synthesis and (ii) one encoding alcohol dehydrogenase (rADH1). These were stereotaxically microinjected into the brain ventral tegmental area (VTA) of Wistar-derived rats bred for generations for their high alcohol preference (UChB), which were allowed access to an ethanol solution and water. Microinjection into the VTA of the lentiviral vector encoding the anticatalase shRNA virtually abolished (-94% p < 0.001) the voluntary consumption of alcohol by the rats. Conversely, injection into the VTA of the lentiviral vector coding for ADH greatly stimulated (2 to 3 fold p < 0.001) their voluntary ethanol consumption. The study strongly suggests that to generate reward and reinforcement, ethanol must be metabolized into acetaldehyde in the brain. Data suggest novel targets for interventions aimed at reducing chronic alcohol intake.

Drinking Motives in Female Smokers: Factor Structure, Alcohol Dependence, and Genetic Influences

Alcohol and tobacco use often co-occur. Human and animal studies indicate that nicotine increases alcohol's rewarding effects and the motivation to consume it. The aims of this study were to examine whether the factorial architecture of self-reported motivations to consume alcohol differed between regular and nonregular cigarette smokers while taking into account the lifetime history of alcohol dependence and psychopathology, and to estimate the genetic and environmental influences on the motivations. Using data on 2,189 monozygotic and dizygotic female twins, we examined the factorial structure (item thresholds and factor loadings, means, and variances) of the items from the Drinking Motives Questionnaire (DMQ) in regular and nonregular smokers. Post hoc tests examined the association between the latent drinking motives factors and alcohol dependence in both groups. Twin models were fitted to the latent drinking motives factors, testing for variations in the magnitude of additive genetic, shared, and nonshared environmental influences between the groups. The 4 DMQ factors (social, conformity, coping, and enhancement) were recovered in both groups, and their measurement structure was consistent across the groups. Regular smokers reported higher levels of coping, enhancement, and social motives while nonregular smokers reported higher conformity motives. Alcohol dependence was associated with higher scores on all motives in both groups; however, in a regression analysis that included all of the motives as predictor variables, only coping was significantly related to alcohol dependence. While twin models revealed evidence for substantially greater genetic influences on enhancement (h² = 0.40), coping (h² = 0.35) and social (h² = 0.37) drinking motives in regular compared to nonregular smokers, the power to statistically distinguish the 2 groups was low. While the measurement structure of the drinking motive factors appears to be similar across regular and nonregular smokers, regular smokers report more motivation to drink for internal affect-related reasons and to obtain social reward. Of all the motives, coping was the most robust predictor of alcohol dependence in both the regular and the nonregular smokers. Further, genetic influences might play a larger role in drinking motives among regular smokers, which provides tentative evidence for latent genetic × smoking status interactions.

Nalmefene for treatment of alcohol dependence

Importance of the field: Alcohol use and dependence are frequent disorders. Despite numerous established psychosocial approaches, relapse to heavy drinking is common in alcohol-dependent patients after detoxification and relapse prevention remains a significant medical challenge.Areas covered in this review: The opioidergic system plays a crucial role in mediating the rewarding effects of alcohol, in part by modulating dopaminergic neurotransmission in mesolimbic brain areas. This review will discuss the neurochemical basis of alcoholism with respect to the opiodergic system. Nalmefene is an alternate opioid receptor that also targets the kappa opioid receptors and thus offers a different treatment approach. The treatment studies conducted so far are discussed.What the reader will gain: We present a comprehensive overview of the implication of the opioidergic system in mediating the rewarding effects of alcoholism and the preclinical and clinical studies conducted so far with nalmefene.Take home message: Although the number of clinical studies conducted with naltrexone by far exceeds the number conducted with nalmefene, the four studies on nalmefene published so far may indicate a role of this opioid antagonist in the treatment of alcoholism. Results of some ongoing studies on nalmefene will provide additional data on its use for this indication.

Alterations in Homocysteine Metabolism Among Alcohol Dependent Patients - Clinical, Pathobiochemical and Genetic Aspects

Addiction research focusing on homocysteine metabolism and its association with aspects of alcohol dependence has revealed important findings. Recent literature on this topic has been taken into account for the review provided. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the homocysteine metabolism. Plasma homocysteine levels are influenced by the single-nucleotide polymorphism (SNP) MTHFR C677T. Besides genetic factors, environmental factors have an impact on homocysteine plasma levels too. Thus, chronic alcohol intake is associated with elevated homocysteine plasma concentrations. Elevation of plasma homocysteine concentration is considered as a predictor for the occurrence of alcohol withdrawal seizures and--as homocysteine is a cardiovascular risk factor--might contribute to the higher risk for myocardial infarction among alcohol dependent patients. Homocysteine acts as an N-methyl-D-aspartate (NMDA) receptor agonist and has excitotoxic effects. Furthermore, it has been demonstrated that homocysteine has neurotoxic effects especially on dopaminergic neurons. As the rewarding effects of alcohol are mediated by the dopaminergic system, a homocysteine-dependent impairment of the reward system possibly leads to an altered drinking behaviour according to the deficit hypothesis of addiction. Homocysteine is involved in the metabolism of methyl groups and DNA-methylation plays a role in regulation of gene expression. Therefore it has been suggested that homocysteine is an important epigenetic factor. It remains to be determined whether alcohol dependent patients benefit from homocysteine lowering strategies, e.g., via supplementation of folate, vitamin B6 and B12. In this respect it is not clear yet, if a supplementation therapy can reduce the risk for the occurrence of alcohol withdrawal seizures.