• Energy Research
• 2016-2025close
• clinical medicine close
• University of Toronto close

Alcoholism and alcohol abuse represent a significant medical and societal problem, and have been thoroughly investigated in humans as well as using animal models. A less well understood aspect of alcohol related disorders is the possible effect of this drug on offspring whose parents were exposed prior to conception. The zebrafish has been successfully employed in alcohol research, however, the effect of exposing the parents to alcohol before fertilization of the eggs on offspring has not been demonstrated in this species. In this proof of concept study, we attempt to address this hiatus. We exposed both adult male and female zebrafish to 0.0% (control) or 0.5% (vol/vol) alcohol chronically for 7 days, subsequently bred the fish within their respective treatment group, collected the fertilized eggs, allowed them to develop, and tested the behavior of free-swimming offspring at their age of 7-9 days post-fertilization. We conducted the analysis in two genetically distinct quasi-inbred strains of zebrafish, AB and TL. Although gross morphology and general activity of the fish appeared unaffected, we found significant behavioral alterations in offspring of alcohol exposed parents compared to offspring of control parents in both strains. These alterations included robustly increased duration and reduced frequency of immobility, increased turn angle, and increased intra-individual variance of turn angle in offspring of alcohol exposed parents in both strains. The mechanisms underlying these behavioral effects or whether the effects are due to exposure of the father, the mother, or both to alcohol are unknown. Nevertheless, our results now set the stage for future studies with zebrafish that will address these questions.

AbstractAimsTo examine how standard analytical approaches to model mortality outcomes of alcohol use compare to the true results using the impact of the March 2017 alcohol taxation increase in Lithuania on all-cause mortality as an example.MethodsFour methodologies were used: two direct methodologies: (a) interrupted time-series on mortality and (b) comparing predictions based on time-series modeling with the real number of deaths for the year following the implementation of the tax increase; and two indirect methodologies: (c) combining a regression-based estimate for the impact of taxation on alcohol consumption with attributable-fraction methodology and (d) using price elasticities from meta-analyses to estimate the impact on alcohol consumption before applying attributable-fraction methodology.Results and ConclusionsWhile all methodologies estimated reductions in all-cause mortality, especially for men, there was substantial variability in the level of mortality reductions predicted. The indirect methodologies had lower predictions as the meta-analyses on elasticities and risk relations seem to underestimate the true values for Lithuania. Directly estimated effects of taxation based on the actual mortalities seem to best represent the true reductions in alcohol-attributable mortality. A significant increase in alcohol excise taxation had a marked impact on all-cause mortality in Lithuania.

Background: Sodium oxybate (SMO) has been shown to be effective in the maintenance of abstinence (MoA) in alcohol-dependent patients in a series of small randomized controlled trials (RCTs). These results needed to be confirmed by a large trial investigating the treatment effect and its sustainability after medication discontinuation. Aims: To confirm the SMO effect on (sustained) MoA in detoxified alcohol-dependent patients. Methods: Large double-blind, randomized, placebo-controlled trial in detoxified adult alcohol-dependent outpatients (80% men) from 11 sites in four European countries. Patients were randomized to 6 months SMO (3.3–3.9 g/day) or placebo followed by a 6-month medication-free period. Primary outcome was the cumulative abstinence duration (CAD) during the 6-month treatment period defined as the number of days with no alcohol use. Secondary outcomes included CAD during the 12-month study period. Results: Of the 314 alcohol-dependent patients randomized, 154 received SMO and 160 received placebo. Based on the pre-specified fixed-effect two-way analysis of variance including the treatment-by-site interaction, SMO showed efficacy in CAD during the 6-month treatment period: mean difference +43.1 days, 95% confidence interval (17.6–68.5; p = 0.001). Since significant heterogeneity of effect across sites and unequal sample sizes among sites ( n = 3–66) were identified, a site-level random meta-analysis was performed with results supporting the pre-specified analysis: mean difference +32.4 days, p = 0.014. The SMO effect was sustained during the medication-free follow-up period. SMO was well-tolerated. Conclusions: Results of this large RCT in alcohol-dependent patients demonstrated a significant and clinically relevant sustained effect of SMO on CAD. Trial registration: ClinicalTrials.gov Identifier: NCT04648423

Zebrafish have become a popular animal model for studying the development of alcohol addiction. Several behavioral paradigms for studying alcohol addiction have been developed for zebrafish, including conditioned place preference, alcohol-induced tolerance, and withdrawal. However, alcohol choice preference tasks have not been established in zebrafish as of yet. The ability of zebrafish to detect alcohol in their environment is required in alcohol choice or preference tasks. To our knowledge, it is currently unknown whether zebrafish are able to detect alcohol in their environment immediately following bath immersion. In the current study, we analyzed the time course of alcohol-induced behavioral changes of zebrafish while being immersed in alcohol solution in a 1.5 L tank. We recorded each trial in high-definition and quantified behavioral responses using automated video tracking-based and manual observation-based methods to quantify temporal changes in alcohol-induced behaviors. As alcohol is known to require several minutes of bath immersion to reach the brain in zebrafish, we argued that behavioral responses before this time point would prove zebrafish's ability to detect this substance in the water. Our results show that a 60-min exposure to 1% alcohol alters behavioral responses in a time-dependent manner. Notably, alcohol exposure significantly increased absolute turn angle, decreased distance to bottom, and variance of distance to bottom within the first 3 min immediately following exposure, a response that occurred before alcohol could reach the brain of the subjects in measurable amounts. These results imply that zebrafish are able to detect alcohol in their environment immediately following immersion into the drug solution.

Alcohol and nicotine (in the form of tobacco) are often taken together, with increased negative health consequences. Co-use may modify intake of one or both of the drugs, or the effects of drugs used to treat nicotine or alcohol addiction. Varenicline is commonly prescribed as an aid to enhance quitting smoking. More recently it has been shown to reduce alcohol intake in humans and laboratory animals. There is little work investigating the role of co-exposure to alcohol and nicotine in the effects of varenicline. In pilot clinical studies, it has been reported that smoking enhances varenicline's effectiveness as a treatment for alcohol misuse, but this relationship has not been systematically investigated. To help resolve this, we examined if the effects of varenicline on alcohol and nicotine self-administration (SA) in rats are modified when the two drugs are taken together. Rats were trained on alcohol SA, and some were implanted with i.v. catheters for nicotine SA. Groups of animals then lever pressed for alcohol or nicotine alone, and another group lever pressed for alcohol and nicotine, using a two lever choice procedure. Varenicline did not affect alcohol SA. Varenicline reduced nicotine SA modestly. Access to both alcohol and nicotine reduced self-administration of either drug, but did not change the effects of varenicline. We found that in rats with a history of alcohol SA, varenicline reduced reinstatement of extinguished alcohol seeking induced by exposure to an alcohol prime combined with cues previously associated with alcohol.

ObjectivesWe aimed to develop a systematic synthesis of systematic reviews of health impacts of climate change, by synthesising studies’ characteristics, climate impacts, health outcomes and key findings.DesignWe conducted an overview of systematic reviews of health impacts of climate change. We registered our review in PROSPERO (CRD42019145972). No ethical approval was required since we used secondary data. Additional data are not available.Data sourcesOn 22 June 2019, we searched Medline, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, Cochrane and Web of Science.Eligibility criteriaWe included systematic reviews that explored at least one health impact of climate change.Data extraction and synthesisWe organised systematic reviews according to their key characteristics, including geographical regions, year of publication and authors’ affiliations. We mapped the climate effects and health outcomes being studied and synthesised major findings. We used a modified version of A MeaSurement Tool to Assess systematic Reviews-2 (AMSTAR-2) to assess the quality of studies.ResultsWe included 94 systematic reviews. Most were published after 2015 and approximately one-fifth contained meta-analyses. Reviews synthesised evidence about five categories of climate impacts; the two most common were meteorological and extreme weather events. Reviews covered 10 health outcome categories; the 3 most common were (1) infectious diseases, (2) mortality and (3) respiratory, cardiovascular or neurological outcomes. Most reviews suggested a deleterious impact of climate change on multiple adverse health outcomes, although the majority also called for more research.ConclusionsMost systematic reviews suggest that climate change is associated with worse human health. This study provides a comprehensive higher order summary of research on health impacts of climate change. Study limitations include possible missed relevant reviews, no meta-meta-analyses, and no assessment of overlap. Future research could explore the potential explanations between these associations to propose adaptation and mitigation strategies and could include broader sociopsychological health impacts of climate change.

AbstractThe serotonin (5‐HT) system has been implicated in the pathophysiology of alcohol (ethanol; EtOH) use disorders. Lorcaserin, a 5‐HT2C receptor agonist, attenuates drug self‐administration in animal models. We investigated the effects of lorcaserin on EtOH intake using the drinking‐in‐the‐dark (DID) procedure, an animal model of binge‐like drinking. We compared the effects of lorcaserin to those of the Food and Drug Administration (FDA)‐approved drug naltrexone and examined the effects of combining lorcaserin and naltrexone. To examine whether effects were specific for EtOH, we examined the effects of lorcaserin and naltrexone, administered alone and in combination, on saccharin intake. Adult male C57BL/6J mice received EtOH access (20% v/v) for 2 h in the home‐cage during the first 3 days of the DID procedure, beginning 3 h into the dark cycle. On day 4, mice were injected with lorcaserin, naltrexone, or a combination of lorcaserin and naltrexone prior to a 4‐h EtOH access. Intake was measured at 2 and 4 h. Lorcaserin reduced EtOH intake in a dose‐dependent fashion over the 2‐ and 4‐h measurement periods. Naltrexone also reduced EtOH intake when administered alone, with dose‐dependent effects being more pronounced over 2 h rather than the full 4‐h session. Combining lorcaserin and naltrexone reduced binge‐like EtOH drinking to a greater extent than either drug alone. A similar pattern of results was obtained for saccharin intake. These results suggest that lorcaserin and naltrexone can have additive effects on binge‐like EtOH drinking. They also support continued research into the therapeutic potential of lorcaserin for alcohol use disorders.