Role In Alcohol Dependence Research Articles

Alcohol abuse and related factors in Asia

Alcohol problems are a global issue, and the nature of alcohol abuse is very complicated. The susceptibility to alcohol abuse varies greatly from one individual to another and also from one nation to another, depending on the availability of alcohol, a country's regulation related to alcohol, a country's cultural background, religious tradition and its economics. Alcohol dependence is also a complicated disease process. The prevalence of alcohol dependence also varies greatly from one ethnic group to another. Asia is the world's largest and most populous continent. The natural disasters, religious conflicts as well as political disputes cause people lack of opportunity in many countries. People in this region do not consume more alcohol than the people in the rest of the world. The prevalence of alcohol dependence is not as high as is seen in other regions. In Asia, not only socio-economic factors, but also biological factors influence drinking behaviour. Findings of functional genetic polymorphism of the major alcohol metabolizing enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) have led to the suggestion that this enzyme system may possibly play a diverse but critical role in alcohol dependence and in the alcohol-related disease process in the different ethnic groups. This paper reviews alcohol problems and related factors. Their management and prevention strategy are discussed.

Naltrexone과 ondansetron의 병합투여가 C57BL/6형 생쥐의 알코올 섭취량에 미치는 영향

알코올 의존의 음주 행동에 VTA에서 NA로 뻗어 있는 도파민 대뇌 보상 경로가 중요하다. 이러한 경로의 토파민 활성도가 <TEX>$5-HT_3$</TEX>계 신경에 의하여 조정되고 있으며, <TEX>$5-HT_3$</TEX> 수용체 길항제인 ondansetron (OND)이 알코올리즘 환자에서 음주량을 감소시키고 금주률을 높인다는 보고가 있다. 이에 생쥐의 섭취량에 대하여 <TEX>$5-HT_3$</TEX> 수용체 길항제인 ondansetron의 투여 효과와, 이러한 ondansetron 및 비 특이적 아편계 수용체 길항제인 naltrexone (NTX)과의 병합 투여 효과를 검증하는데 목적이 있다. 알코올 의존화 된 C57BL/6형 수컷 생쥐를 4군으로 나눈 뒤, 10일간 각 군에 vehicle, OND 0.01 mg/kg 단독, NTX 1.0 mg/kg 단독, 및 OND 0.01 mg/kg과 NTX 1 mg/kg 병합 투여하면서 2시간 알코올의 섭취량, 22시간 물 섭취량, 24시간 사료 섭취량 및 체중을 조사하였다. 본 연구의 결과로 2시간 알코올 섭취량의 10일간 변화에 대해 vehicle 투여 군과 나머지 3군의 약물 투여군과 repeated measure ANOVA를 이용하여 각각 비교하였을 때, vehicle 투여군과 NTX 단독 투여군간에 유의한 교차가 관찰되었으나 (p=0.042), OND 단독 투여군과 NTX과 OND 병합 투여군은 vehicle 투여군과 유의한 차이가 없었다. 일별 2시간 알코올 섭취량에 대하여 NTX 투여군과 vehicle 투여군의 군간 비교시 vehicle 투여군에 비하여 NTX 투여군에서 약물 투여 4일부터 10일까지 유의하게 감소하였다(4일 p=0.010; 6일 p=0.050; 8일 p=0.017; 10일 p=0.005). 그리고 NTX과 OND 병합 투여군과 vehicle 투여군의 양군을 비교하였을 때에는 2시간 알코올 섭취량이 4일과 10일에만 유의하게 감소하였다(4일 p=0.049; 10일 p=0.022). 그러나 22시간 물 섭취량, 24시간 사료 섭취량 및 체중의 10일간 변화에 대해 vehicle 투여군과 나머지 3 군의 약물 투여군과의 repeated measure ANOVA를 이용하여 각각 비교하였을 때, 모두 유의한 교차효과가 없었다. 이상의 결과는 생쥐의 섭취량에 대하여 OND의 투여 효과는 없었으며, OND과 NTX의 병합 투여시에는 NTX의 알코올의 섭취량 억제 효과가 감소되었다. 따라서 앞으로 <TEX>$5-HT_3$</TEX> 신경계와 도파민 및 아편 신경계와의 상관관계에 대한 연구가 필요할 것으로 생각된다. Dopamine reward pathway projecting from ventral tegmental area to nucleus accumbens is well known as playing an important role in alcohol dependence. It is supposed that this dopamine pathway is modulated by <TEX>$5-HT_3$</TEX> nervous system, and it was reported that ondansetron (OND), <TEX>$5-HT_3$</TEX> receptor antagonist, reduced drinking amount and increased abstinence rate in alcohol-dependent patients. The purpose of this study is to investigate the effect of combination of OND and naltrexone (NTX), non-specific opioid receptor antagonist, on alcohol intake in C57BL/6 mice. In 40 C57BL/6 mice in the state of alcohol dependence, vehicle, while OND 0.01 mg/kg, or NTX 1.0 mg/kg administrated respectively, or OND 0.01 mg/kg and NTX 1.0 mg/kg administrated simultaneously for ten days, medication effects on 2-hr alcohol, 22-hr water, 24-hr food intake and body weight were studied. When vehicle group was compared with 3 medication groups respectively, using a repeated measure ANOVA, NTX alone and vehicle groups showed a significant medication by time interaction (p=0.042) in 2-hr alcohol intake, but in the other 2 groups, OND and NTX combination group and OND alone group, there was no significant interaction with vehicle group in 2-hr alcohol intake. From these results, it is suggested that there is no effect on alcohol intake in mice treating with OND, and naltrexone#s suppression effect on alcohol intake in mice is attenuated when treating with OND and NTX simultaneously. It is supposed that a further study looking at the interactions of serotonin, dopamine and opioid nerves systems will be needed.

Family Response to Adults and Alcohol

SUMMARY Studies indicate that couple and family relationships play a significant role in alcohol dependence and recovery processes, yet a relational framework in alcoholism treatment and research paradigms remains largely absent. Reciprocal, interactive dynamics between the alcoholic and couple-family relationships suggests the need for a more comprehensive conceptualization of alcoholism, inclusive of a relational perspective in addition to the current individual emphasis on abstinence as the defining measurement of successful treatment. Family variables, especially the couple relationship, underscore the importance of the concept of “couple recovery.” Bridging the gap between individual and couple recovery requires: multiple levels of intervention, developmentally appropriate strategies through the stages of recovery, and openness to integrating various therapeutic approaches. The Couples Reciprocal Development Approach (CRDA), a theory of long-term couple recovery from alcoholism, identifies three distinct but interactive components of couple functioning.

Suicidal behavior among adolescents with conduct disorder—the role of alcohol dependence

Our aim was to investigate the association between alcohol dependence and suicidal behavior among adolescent girls and boys suffering from conduct disorder (CD). The original study sample consisted of 387 adolescents (age 12–17) admitted to psychiatric inpatient care between April 2001 and May 2005. DSM-IV-based psychiatric diagnoses and variables measuring suicidal behavior were obtained from the Schedule for Affective Disorders and Schizophrenia for School Aged Children—Present and Lifetime (K-SADS-PL). Of the total study population, 59 adolescent girls and 82 boys had CD according to DSM-IV criteria. Of all adolescents with CD, 24 (40.7%) girls and 24 (29.3%) boys were suffering from alcohol dependence. Among girls with CD, alcohol dependence increased the risk for suicide attempts up to 3.8-fold (95% CI 1.1–13.4). Among boys with CD, alcohol dependence increased the risk for life-threatening suicide attempt over nine-fold (95% CI 1.2–80.1). In addition, the risk for self-mutilative behavior was as high as 3.9-fold (95% CI 1.1–13.8) among girls and 5.3-fold (95% CI 1.1–26.5) among boys. The results indicate that, among adolescents suffering from CD, the risk of suicidal behavior is considerably increased by co-morbid alcohol dependence, which should therefore be carefully taken into account in clinical work.

Alkoholbedingte Störungen - Ätiopathogenese und therapeutischer Ausblick

The scientific understanding of the neurobiological priniciples of alcoholism has made significant progress in recent years. Especially the effects of ethanol on the neurotransmitter-systems are well studied. Dopaminergic and GABAergic facilitation contribute to the stimulating effects of low doses of alcohol while many of its adverse effects are mediated by glutamatergic inhibition at higher doses. A reduced serotonine-metabolism was shown to be a risk factor for the development of an alcohol dependence. The historic success of absinthe is discussed in this context. Absinthe is a mixture of ethanol and thujone, a substance that leads to a GABAergic inhibition as well as a reduced serotonergic responsiveness. Many studies substantiate the role of cannabinoid as well as striatal opiate-receptors in alcohol-related disorders. Neuroimaging studies could prove the important role of the reward system in this connection. Genetic factors were shown to be predisposing, however biological and environmental factors have a regulatory effect on the gene expression. Disturbances of the hpa-axis (hypothalamus-pituitary gland-adrenal cortex) were also shown to play a role in alcohol dependence. The understanding of these neurobiological principles of alcohol-related disorders should contribute to enhance and improve their therapeutic options.

No association of the GABAA receptor genes on chromosome 5 with alcoholism in the collaborative study on the genetics of alcoholism sample

A substantial body of literature suggests that gamma-aminobutyric acid (GABA) may be involved in the neurochemical pathways contributing to alcohol use and related disorders. Chromosome 5 contains a cluster of GABA(A) receptor genes, GABRA1, GABRA6, GABRB2, and GABRG2, which have been among the most extensively studied in relation to alcohol use. These studies have yielded mixed results. Using data from large, multiplex alcoholic families collected as part of the Collaborative Study on the Genetics of Alcoholism (COGA), we sought to provide more conclusive evidence regarding the role of the GABA(A) receptor genes on chromosome 5. Multiple single nucleotide polymorphisms (SNPs) were tested in each of the four chromosome 5q GABA(A) receptor genes, and we conducted both classic trio-based association analyzes and extended pedigree analyzes. We found no consistent evidence of association with alcohol dependence or alcohol dependence comorbid with antisocial personality disorder (ASPD) for any of the regions tested in the chromosome 5 GABA(A) receptor genes. These analyses suggest that the GABA(A) receptor genes on chromosome 5 do not play a strong role in alcohol dependence. Future studies are planned to test whether these genes are more important in influencing behavioral endophenotypes related to the risk of alcohol dependence.

Amisulpride Does Not Prevent Relapse in Primary Alcohol Dependence: Results of a Pilot Randomized, Placebo‐Controlled Trial

Background Few medications have been proved to be effective in preventing relapse in alcoholism. The mesolimbic dopamine system is known to play an important role in alcohol dependence. Amisulpride, a substituted benzamide, seems to facilitate dopaminergic neurotransmission at low doses.Methods After short‐term, inpatient detoxification, 71 patients participated in a randomized, double‐blind, placebo‐controlled study to evaluate the efficacy of amisulpride in relapse prevention. Patients received amisulpride 50 mg/day or placebo for 6 months.Results There were no differences between the two groups of treatment for time to first drink, length of time before dropout, number of drinking days, and number of heavy drinking days. However, significantly more patients who were treated with amisulpride than those who were treated with placebo were nonabstinent and had relapsed at each visit. Craving for alcohol was significantly higher in the amisulpride than in the placebo group. Transaminases, γ‐glutamyl‐transferase, and mean erythrocyte corpuscular volume were regularly higher in the amisulpride group than in the placebo group.Conclusions The results indicate that treatment with amisulpride was not effective in preventing relapse to drinking in detoxified, alcohol‐dependent patients. The significance of this finding is discussed, particularly in terms of the effects of neuroleptics on alcohol consumption.

No association of CCK and CCK B receptor polymorphisms with alcohol dependence

Cholecystokinin (CCK) is the most widely distributed neuropeptide in the central nervous system. One of its several functions is to modulate the release of dopamine in brain areas involved in reinforcement and reward behavior. The aim of this study was to investigate the association of CCK system genes (CCK, CCK A and CCK B receptor genes) with alcohol dependence using single nucleotide polymorphisms (SNPs) as genetic markers. A total of 257 psychiatrically interviewed Finns were genotyped for CCK (-45C>T), CCK A (Val365Ile) and CCK B (Val125Ile) receptor polymorphisms. Allele frequencies were compared between 150 unrelated healthy Finnish controls and 107 unrelated alcohol-dependent subjects (DSM-III-R criteria), who were also criminal offenders. The frequency of the CCK -45T allele was not significantly different between controls [0.07] and alcoholics [0.09]. The CCK B receptor polymorphism Val125Ile was also not associated with alcoholism and the Ile125 allele frequencies were 0.05 in controls vs. 0.06 in alcohol-dependent subjects. A CCK A receptor marker, Val365Ile, was uninformative in this Finnish dataset; all subjects were Val365/Val365 homozygous. The results suggest that CCK -45C>T and CCKBR Val125Ile polymorphisms do not have a major role in alcohol dependence in the population studied. The role of the CCK A the receptor in alcohol dependence remains open until additional DNA sequence variants for this gene become available.

Role of glutamatergic and GABAergic systems in alcoholism.

The pharmacological effects of ethanol are complex and widespread without a well-defined target. Since glutamatergic and GABAergic innervation are both dense and diffuse and account for more than 80% of the neuronal circuitry in the human brain, alterations in glutamatergic and GABAergic function could affect the function of all neurotransmitter systems. Here, we review recent progress in glutamatergic and GABAergic systems with a special focus on their roles in alcohol dependence and alcohol withdrawal-induced seizures. In particular, NMDA-receptors appear to play a central role in alcohol dependence and alcohol-induced neurological disorders. Hence, NMDA receptor antagonists may have multiple functions in treating alcoholism and other addictions and they may become important therapeutics for numerous disorders including epilepsy, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's chorea, anxiety, neurotoxicity, ischemic stroke, and chronic pain. One of the new family of NMDA receptor antagonists, such as DETC-MESO, which regulate the redox site of NMDA receptors, may prove to be the drug of choice for treating alcoholism as well as many neurological diseases.

Chronic ethanol increases N-methyl-D-aspartate-stimulated nitric oxide formation but not receptor density in cultured cortical neurons.

The effects of prolonged ethanol exposure on excitatory amino acid receptor stimulated nitric oxide (NO) formation were examined in primary rat cortical neuronal cultures. Chronic ethanol (4 days, 100 mM) potentiated N-methyl-D-aspartate (NMDA)-stimulated NO formation as determined by measuring the conversion of [3H]arginine to [3H]citrulline. In contrast, chronic ethanol had no effect on NO formation stimulated by kainate, alpha-amino-3-hydroxy-5-methyl-4-isoxalonepropionic acid, or the calcium ionophore ionomycin. Potassium chloride-stimulated NO formation was also enhanced by chronic ethanol treatment, but this effect was not seen in the presence of the ionotropic glutamate receptor antagonists MK-801 and 6-cyano-7-nitroquinoxaline-2,3-dione. Immunoblot analysis of expression of NR1, NR2A, and NR2B receptor subunits showed no difference between control and chronic ethanol-treated cultures. In support of this apparent lack of change in receptor density, there was no difference in the specific binding of 125I-MK-801 between control and chronic ethanol-treated groups. These results demonstrate that prolonged ethanol exposure selectively enhanced NMDA receptor-stimulated NO formation, which may play an important role in alcohol dependence, withdrawal, and alcohol-associated brain damage. These results also suggest that chronic ethanol-induced increases in NMDA receptor function may not be due to a simple increase in the number of NMDA receptors or change in NMDA receptor subunit composition but may instead reflect more complicated and subtle changes.