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- Augier, Eric
(författare)
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Recent Advances in the Potential of Positive Allosteric Modulators of the GABA(B) Receptor to Treat Alcohol Use Disorder
- 2021
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Ingår i: Alcohol and Alcoholism. - : Oxford University Press. - 0735-0414 .- 1464-3502. ; 56:2, s. 139-148
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The effects of alcohol on gamma-aminobutyric acid (GABA) transmission are key for the development and maintenance of alcohol use disorder (AUD). Previous research consistently indicates that GABA(B) receptor agonists such as baclofen can attenuate addiction-related behaviors in preclinical models of AUD. More importantly, baclofen has also shown promise in clinical studies, particularly in severely alcohol-dependent patients. However, despite this promise, other clinical studies have not confirmed its efficacy and chiefly, larger clinical trials have not been conducted. Therefore, with the exception of France, baclofen is not approved for the treatment of AUD in any other country. Furthermore, it is also important to keep in mind that some patients treated with baclofen may experience important side-effects, including sedation, drowsiness and sleepiness. Methods: This short review will first discuss the history of baclofen for AUD treatment. We will then summarize preclinical behavioral results that have investigated the efficacy of GABA(B) PAMs for addiction treatment, with a special focus on our recent work that investigated the effects of ADX71441, a novel GABA(B) PAM, on several alcohol-related behaviors in rats that model important aspects of human AUD. Finally, in light of the recent criticism about the translational value of animal models of addiction, the specific translational potential of our work and of other preclinical studies that have unanimously reported the efficacy of GABA(B) PAMs to attenuate multiple alcohol-related behaviors will be discussed. Results: Positive allosteric modulators (PAMs) of the GABA(B) receptor offer an attractive alternative approach to baclofen and have the potential to achieve mechanistic and therapeutic effects similar to GABA(B) agonists, while avoiding the tolerance and toxicity issues associated with baclofen. To date, all preclinical behavioral results have invariably shown the efficacy of GABA(B) PAMs for addiction treatment. Conclusions: Preclinical studies indicate that GABA(B) PAMs have a higher therapeutic index than orthosteric agonists, at least in terms of mitigating the sedative effects of GABA(B) agonism. This predicts that GABA(B) PAMs have a high translational potential in humans and merit being tested clinically, in particular in patients with severe AUD.
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| 12. |
- Baburin, Aleksei, et al.
(författare)
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Age, Period and Cohort Effects On Alcohol Consumption In Estonia, 1996-2018
- 2021
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Ingår i: Alcohol and Alcoholism. - : Oxford University Press. - 0735-0414 .- 1464-3502. ; 56:4, s. 451-459
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To analyse the independent effects of age, period and cohort on estimated daily alcohol consumption in Estonia.METHODS: This study used data from nationally representative repeated cross-sectional surveys from 1996 to 2018 and included 11,717 men and 16,513 women aged 16-64 years in total. The dependent variables were consumption of total alcohol and consumption by types of beverages (beer, wine and strong liquor) presented as average daily consumption in grams of absolute alcohol. Mixed-effects negative binomial models stratified by sex were used for age-period-cohort analysis.RESULTS: Alcohol consumption was highest at ages 20-29 years for both men and women and declined in older ages. Significant period effects were found indicating that total alcohol consumption and consumption of different types of beverages had increased significantly since the 1990s for both men and women. Cohort trends differed for men and women. Men born in the 1990-2000s had significantly lower daily consumption compared to earlier cohorts, whereas the opposite was found for women.CONCLUSION: While age-related patterns of alcohol consumption are aligned with life course stages, alcohol use has increased over the study period. Although the total daily consumption among men is nearly four times higher than among women, the cohort trends suggest convergence of alcohol consumption patterns for men and women.
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| 13. |
- Balldin, Jan, 1935, et al.
(författare)
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TAQ1A1 Allele of the DRD2 Gene Region Contribute to Shorter Survival Time in Alcohol Dependent Individuals When Controlling for the Influence of Age and Gender. A Follow-up Study of 18 Years.
- 2018
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Ingår i: Alcohol and Alcoholism. - : Oxford University Press (OUP). - 1464-3502 .- 0735-0414. ; 53:3
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the influence of the A1 allele of the TAQ1A polymorphism in the dopamine D2 receptor (DRD2) gene region on mortality in adult individuals with alcohol dependence.The study sample consisted of 359 alcohol-dependent individuals treated for severe alcohol withdrawal symptoms in 1997. Years of survival was studied in an 18-year follow-up. In the analyses, gender and age were controlled for.At the 18-year follow-up, 53% individuals had deceased. The analyses showed that older age (P < 0.001), male gender (P < 0.05) and carrying the A1 allele (P < 0.01) all significantly and independently contributed to shorten years of survival. Among the deceased individuals, the genotype A1+ was the only significant contributor to shorten years of survival.An important contribution of the present study is that in alcohol dependence the Taq1A1 allele of the DRD2 gene region is a risk factor for premature death of similar importance as the well-known risk factors of age and gender.We investigated the influence of A1 allele of the TAQ1A polymorphism in DRD2 receptor gene region on mortality in alcohol-dependent individuals in an 18-year follow-up. Age, gender and the A1 allele contributed to shorten years of survival. Among the deceased, the A1+ was the only contributor to shorten years of survival.
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| 20. |
- Bendtsen, Preben, et al.
(författare)
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Hazardous drinking concepts, limits and methods : Low levels of awareness, knowledge and use in the Swedish population
- 2011
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Ingår i: Alcohol and Alcoholism. - Oxford, UK : Oxford University Press (OUP). - 0735-0414 .- 1464-3502. ; 46:5, s. 638-645
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To investigate the awareness and knowledge of hazardous drinking limits among the general population in Sweden and the extent to which people estimate their alcohol consumption in standard drinks to assess their level of drinking. Methods: A population-based study involving 6000 individuals selected from the total Swedish population was performed. Data were collected by means of a postal questionnaire. The mail survey response rate was 54.3% (n = 3200) of the net sample of 5891 persons. Results: With regard to drinking patterns, 10% of the respondents were abstainers, 59% were sensible drinkers and 31% were classified as hazardous drinkers. Most of the abstainers (80%), sensible drinkers (64%) and hazardous drinkers (56%) stated that they had never heard about the standard drink method. Familiarity with the hazardous drinking concept also differed between the three categories although 61% of sensible and hazardous drinkers expressed awareness of the concept (46% of the abstainers). Knowledge about the limits for sensible drinking was very poor. Between 94 and 97% in the three categories did not know the limit. There was a statistically significant association between having visited health care within the last 12 months and being aware of the standard drink method and the hazardous drinking concept, but not with knowing the hazardous drinking limits. Similarly, there was a significant association between having had at least one alcohol conversation in health care within the last 12 months and being aware of the standard drink method and the hazardous drinking concept, but not with knowing the hazardous drinking limits. Conclusion: The results can be seen as a major challenge for the health-care system and public health authorities because they imply that a large proportion of the Swedish population does not know when alcohol consumption becomes a threat to their health. The current strategy to disseminate knowledge about sensible drinking limits to the population through the health-care system seems to have failed and new means of informing the population are warranted. © The Author 2011. Published by Oxford University Press on behalf of the Medical Council on Alcohol. All rights reserved.
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