Dataset Information

Triple monoamine uptake inhibitors demonstrate a pharmacologic association between excessive drinking and impulsivity in high-alcohol-preferring (HAP) mice.

ABSTRACT: Approximately 30% of current drinkers in the United States drink excessively, and are referred to as problem/hazardous drinkers. These individuals, who may not meet criteria for alcohol abuse or dependence, comprise binge, heavy drinkers, or both. Given their high prevalence, interventions that reduce the risk of binge and heavy drinking have important public health implications. Impulsivity has been repeatedly associated with excessive drinking in the clinical literature. As impulsivity is correlated with, and may play a critical role in, the initiation and maintenance of excessive drinking, this behavior may be an important target for therapeutic intervention. Hence, a better understanding of pharmacological treatments capable of attenuating excessive drinking and impulsivity may markedly improve clinical outcomes. The high-alcohol-preferring (HAP) mice represent a strong rodent model to study the relationship between impulsivity and excessive alcohol drinking, as recent evidence indicates they consume high levels of alcohol throughout their active cycle and are innately impulsive. Using this model, the present study demonstrates that the triple monoamine uptake inhibitors (TUIs) amitifadine and DOV 102, 677 effectively attenuate binge drinking, heavy drinking assessed via a 24-hour free-choice assay, and impulsivity measured by the delay discounting procedure. In contrast, 3-PBC, a GABA-A ?1 preferring ligand with mixed agonist-antagonist properties, attenuates excessive drinking without affecting impulsivity. These findings suggest that in HAP mice, monoamine pathways may predominate as a common mechanism underlying impulsivity and excessive drinking, while the GABAergic system may be more salient in regulating excessive drinking. We further propose that TUIs such as amitifadine and DOV 102, 677 may be used to treat the co-occurrence of impulsivity and excessive drinking.

SUBMITTER: O'Tousa DS

PROVIDER: S-EPMC3984927 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Triple monoamine uptake inhibitors demonstrate a pharmacologic association between excessive drinking and impulsivity in high-alcohol-preferring (HAP) mice.

O'Tousa David S DS Warnock Kaitlin T KT Matson Liana M LM Namjoshi Ojas A OA Linn Michael Van MV Tiruveedhula Veera Venkata VV Halcomb Meredith E ME Cook James J Grahame Nicholas J NJ June Harry L HL

Addiction biology 20131013 2

Approximately 30% of current drinkers in the United States drink excessively, and are referred to as problem/hazardous drinkers. These individuals, who may not meet criteria for alcohol abuse or dependence, comprise binge, heavy drinkers, or both. Given their high prevalence, interventions that reduce the risk of binge and heavy drinking have important public health implications. Impulsivity has been repeatedly associated with excessive drinking in the clinical literature. As impulsivity is corr ...[more]

PMID: 24118509

Similar Datasets

Project description:Numerous work-related drinking mechanisms have been posited and, oftentimes, examined in isolation. We combined data from over 100 occupational attributes into several factors and tested the association of these factors with measures of alcohol use. We used the NLSY79 2006 wave, a U.S. representative sample of 6426 workers ages 41 to 49 and the 2006 Occupational Information Network database (O*NET), a nationally representative sample of nearly 1000 occupations. We conducted exploratory factor analysis on 119 occupational attributes and found three independent workplace characteristics - physical demands, job autonomy, and social engagement - explained the majority of the variation. We then tested the association of these composite attributes with three drinking measures, before and after adjusting for gender, race/ethnicity, and a measure of human capital using count data models. We then stratified by gender and repeated our analyses. Men working in occupations with a one standard deviation higher level of physical demand (e.g. construction) reported a higher number of heavy drinking occasions (+20%, p < 0.05). Job autonomy was not significantly associated with measures of alcohol use and when the combined association of higher levels of physical demand and lower levels of job autonomy was examined, modest support for job strain as a mechanism for work-related alcohol consumption was found. In our pooled sample, working in occupations with one standard deviation higher levels of social engagement was associated with lower numbers of drinking days (-9%, p < 0.05) after adjustment. Physical demand and social engagement were associated with alcohol consumption measures but these relationships varied by workers' gender. Future areas of research should include confirmatory analyses using other waves of O*Net data and replicating the current analysis in other samples of workers. If our results are validated, they suggest male workers in high physical demand occupations could be targets for intervention.

Project description:Increased levels of impulsivity are associated with increased illicit drug use and alcoholism. Previous research in our laboratory has shown that increased levels of delay discounting (a decision-making form of impulsivity) are related to appetitive processes governing alcohol self-administration as opposed to purely consummatory processes. Specifically, the high-seeking/high-drinking alcohol-preferring P rats showed increased delay discounting compared to nonselected Long Evans rats (LE) whereas the high-drinking/moderate-seeking HAD2 rats did not. The P rats also displayed a perseverative pattern of behavior such that during operant alcohol self-administration they exhibited greater resistance to extinction.One explanation for the previous findings is that P rats have a deficit in response inhibition. This study followed up on this possibility by utilizing a countermanding paradigm (stop signal reaction time [SSRT] task) followed by operant self-administration of alcohol across increasing fixed ratio requirements (FR; 1, 2, 5, 10, and 15 responses). In separate animals, 24-hour access 2-bottle choice (10% EtOH vs. water) drinking was assessed.In the SSRT task, P rats exhibited an increased SSRT compared to both LE and HAD2 rats indicating a decrease in behavioral inhibition in the P rats. Also, P rats showed increased operant self-administration across all FRs and the greatest increase in responding with increasing FR requirements. Conversely, the HAD2 and LE had shorter SSRTs and lower levels of operant alcohol self-administration. However, for 2-bottle choice drinking HAD2s and P rats consumed more EtOH and had a greater preference for EtOH compared to LE.These data extend previous findings showing the P rats to have increased delay discounting (decision-making impulsivity) and suggest that P rats also have a lack of behavioral inhibition (motor impulsivity). This supports the notion that P rats are a highly impulsive as well as "high-seeking" model of alcoholism, and that the HAD2s' elevated levels of alcohol consumption are not mediated via appetitive processes or impulsivity.

Dataset Information

Triple monoamine uptake inhibitors demonstrate a pharmacologic association between excessive drinking and impulsivity in high-alcohol-preferring (HAP) mice.

Publications

Triple monoamine uptake inhibitors demonstrate a pharmacologic association between excessive drinking and impulsivity in high-alcohol-preferring (HAP) mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets