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Impaired response inhibition in the rat 5 choice continuous performance task during protracted abstinence from chronic alcohol consumption.

ABSTRACT: Impaired cognitive processing is a hallmark of addiction. In particular, deficits in inhibitory control can propel continued drug use despite adverse consequences. Clinical evidence shows that detoxified alcoholics exhibit poor inhibitory control in the Continuous Performance Task (CPT) and related tests of motor impulsivity. Animal models may provide important insight into the neural mechanisms underlying this consequence of chronic alcohol exposure though pre-clinical investigations of behavioral inhibition during alcohol abstinence are sparse. The present study employed the rat 5 Choice-Continuous Performance Task (5C-CPT), a novel pre-clinical variant of the CPT, to evaluate attentional capacity and impulse control over the course of protracted abstinence from chronic intermittent alcohol consumption. In tests conducted with familiar 5C-CPT conditions EtOH-exposed rats exhibited impaired attentional capacity during the first hours of abstinence and impaired behavioral restraint (increased false alarms) during the first 5d of abstinence that dissipated thereafter. Subsequent tests employing visual distractors that increase the cognitive load of the task revealed significant increases in impulsive action (premature responses) at 3 and 5 weeks of abstinence, and the emergence of impaired behavioral restraint (increased false alarms) at 7 weeks of abstinence. Collectively, these findings demonstrate the emergence of increased impulsive action in alcohol-dependent rats during protracted alcohol abstinence and suggest the 5C-CPT with visual distractors may provide a viable behavioral platform for characterizing the neurobiological substrates underlying impaired behavioral inhibition resulting from chronic intermittent alcohol exposure.

SUBMITTER: Irimia C

PROVIDER: S-EPMC4198178 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Impaired response inhibition in the rat 5 choice continuous performance task during protracted abstinence from chronic alcohol consumption.

Irimia Cristina C Tuong Roxanne N RN Quach Tammy T Parsons Loren H LH

PloS one 20141015 10

Impaired cognitive processing is a hallmark of addiction. In particular, deficits in inhibitory control can propel continued drug use despite adverse consequences. Clinical evidence shows that detoxified alcoholics exhibit poor inhibitory control in the Continuous Performance Task (CPT) and related tests of motor impulsivity. Animal models may provide important insight into the neural mechanisms underlying this consequence of chronic alcohol exposure though pre-clinical investigations of behavio ...[more]

PMID: 25333392

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Project description:Persons with alcoholism who are abstinent exhibit persistent impairments in the capacity for response inhibition, and this form of impulsivity is significantly associated with heightened relapse risk. Brain-imaging studies implicate aberrant prefrontal cortical function in this behavioral pathology, although the underlying mechanisms are not understood. Here we present evidence that deficient activation of glycine and serine release in the ventral medial prefrontal cortex (vmPFC) contributes to increased motor impulsivity during protracted abstinence from long-term alcohol exposure. Levels of 12 neurotransmitters were monitored in the rat vmPFC during the performance of a challenging variant of the five-choice serial reaction time task (5-CSRTT) in which alcohol-exposed rats exhibit excessive premature responding. Following long-term ethanol exposure, rats showed blunted task-related recruitment of vmPFC glycine and serine release, and the loss of an inverse relationship between levels of these neurotransmitters and premature responding normally evident in alcohol-naive subjects. Intra-vmPFC administration of the glycine transport inhibitor ALX5407 prevented excessive premature responding by alcohol-exposed rats, and this was reliant on NMDA glycine site availability. Alcohol-exposed rats and controls did not differ in their premature responding and glycine and serine levels in vmPFC during the performance of the standard 5-CSRTT. Collectively, these findings provide novel insight into cortical neurochemical mechanisms contributing to increased impulsivity following long-term alcohol exposure and highlight the NMDA receptor coagonist site as a potential therapeutic target for increased impulsivity that may contribute to relapse risk.SIGNIFICANCE STATEMENT Persons with alcoholism demonstrate increased motor impulsivity during abstinence; however, the neuronal mechanisms underlying these behavioral effects remain unknown. Here, we took advantage of an animal model that shows deficiencies in inhibitory control following prolonged alcohol exposure to investigate the neurotransmitters that are potentially responsible for dysregulated motor impulsivity following long-term alcohol exposure. We found that increased motor impulsivity is associated with reduced recruitment of glycine and serine neurotransmitters in the ventromedial prefrontal cortex (vmPFC) cortex in rats following long-term alcohol exposure. Administration of glycine transport inhibitor ALX5407 in the vmPFC alleviated deficits in impulse control.

Project description:ObjectivesThe aim of this review was to explore the notion of alcohol-related presenteeism; that is, whether evidence in the research literature supports an association between employee alcohol consumption and impaired work performance.DesignSystematic review of observational studies.Data sourcesMEDLINE, Web of Science, PsycINFO, CINAHL, AMED, Embase and Swemed+ were searched through October 2018. Reference lists in included studies were hand searched for potential relevant studies.Eligibility criteriaWe included observational studies, published 1990 or later as full-text empirical articles in peer-reviewed journals in English or a Scandinavian language, containing one or more statistical tests regarding a relationship between a measure of alcohol consumption and a measure of work performance.Data extraction and synthesisTwo independent reviewers extracted data. Tested associations between alcohol consumption and work performance within the included studies were quality assessed and analysed with frequency tables, cross-tabulations and χ2 tests of independence.ResultsTwenty-six studies were included, containing 132 tested associations. The vast majority of associations (77%) indicated that higher levels of alcohol consumption were associated with higher levels of impaired work performance, and these positive associations were considerably more likely than negative associations to be statistically significant (OR=14.00, phi=0.37, p<0.001). Alcohol exposure measured by hangover episodes and composite instruments were over-represented among significant positive associations of moderate and high quality (15 of 17 associations). Overall, 61% of the associations were characterised by low quality.ConclusionsEvidence does provide some support for the notion of alcohol-related presenteeism. However, due to low research quality and lack of longitudinal designs, evidence should be characterised as somewhat inconclusive. More robust and less heterogeneous research is warranted. This review, however, does provide support for targeting alcohol consumption within the frame of workplace interventions aimed at improving employee health and productivity.Prospero registration numberCRD42017059620.

Project description:This paper presents a descriptive analysis of data gathered by personal interviews from a multistage random sample of 1640 residents aged 18?34 years in Wuhan, China. First, alcohol drinkers and abstainers were compared based on demographic, attitude, and belief variables. Next, the drinkers from the sample were classified into four groups based on frequency-quantity of alcohol use, and the frequency-quantity groups were compared on the same variables. For Abstainers versus Drinkers, we found no difference by age or gender in this sample. Married people and people with children were more likely to be abstainers. University-educated, currently-employed individuals in mid-level jobs were more likely to abstain from alcohol. Vocational/Technical graduates, people who were currently attending college, currently unemployed and never-employed individuals were more likely to be drinkers. Abstainers also responded with less-positive attitudes and beliefs about drinking and attached more importance to reasons for not drinking compared to drinkers. When the drinking frequency-quantity groups were compared, gender differences became significant: more high-quantity drinkers were women; however the guideline for quantity for women was >1 drink at a time compared to >2 drinks at a time for men. Quantity and frequency of drinking was significantly associated with having children, educational level, employment status, and type of occupation. Age, marital status, and being in college did not relate significantly with quantity and frequency of drinking alcohol. Attitudes and beliefs about drinking tended to be more positive among high-frequency and high-quantity drinkers. Drinkers in all frequency-quantity groups attached greater importance to social reasons for drinking compared to personal/psychological reasons for drinking. Drinkers in the lowest frequency-quantity group attached the most importance to reasons for not drinking. These findings confirmed that in China drinking plays an important role in socializing and celebrating, and that there are important differences between alcohol drinkers and abstainers and between frequency/quantity groups of drinkers. Western models of individualized motivation of behaviors may not accurately explain alcohol use in China. We believe the findings from this study suggest the need for more detailed studies of alcohol drinking and abstaining.

Project description:ImportanceAlthough the detrimental effects of alcohol on the brain are widely acknowledged, observed structural changes are highly heterogeneous, and diagnostic markers for characterizing alcohol-induced brain damage, especially in early abstinence, are lacking. This heterogeneity, likely contributed to by comorbidity factors in patients with alcohol use disorder (AUD), challenges a direct link of brain alterations to the pathophysiology of alcohol misuse. Translational studies in animal models may help bridge this causal gap.ObjectiveTo compare microstructural properties extracted using advanced diffusion tensor imaging (DTI) in the brains of patients with AUD and a well-controlled rat model of excessive alcohol consumption and monitor the progression of these properties during early abstinence.Design, setting, and participantsThis prospective observational study included 2 cohorts of hospitalized patients with AUD (n = 91) and Marchigian Sardinian alcohol-preferring (msP) rats (n = 27). In humans cross-sectional comparison were performed with control participants (healthy men [n = 36]) and longitudinal comparisons between different points after alcohol withdrawal. In rats, longitudinal comparisons were performed in alcohol-exposed (n = 27) and alcohol-naive msP rats (n = 9). Human data were collected from March 7, 2013, to August 3, 2016, and analyzed from June 14, 2017, to May 31, 2018; rat data were collected from January 15, 2017, to May 12, 2017, and analyzed from October 11, 2017, to May 28, 2018.Main outcomes and measuresFractional anisotropy and other DTI measures of white matter properties after long-term alcohol exposure and during early abstinence in both species and clinical and demographic variables and time of abstinence after discharge from hospital in patients.ResultsThe analysis included 91 men with AUD (mean [SD] age, 46.1 [9.6] years) and 27 male rats in the AUD groups and 36 male controls (mean [SD] age, 41.7 [9.3] years) and 9 male control rats. Comparable DTI alterations were found between alcohol and control groups in both species, with a preferential involvement of the corpus callosum (fractional anisotropy Cohen d = -0.84 [P < .01] corrected in humans and Cohen d = -1.17 [P < .001] corrected in rats) and the fornix/fimbria (fractional anisotropy Cohen d = -0.92 [P < .001] corrected in humans and d = -1.24 [P < .001] corrected in rats). Changes in DTI were associated with preadmission consumption patterns in patients and progress in humans and rats during 6 weeks of abstinence. Mathematical modeling shows this process to be compatible with a sustained demyelination and/or a glial reaction.Conclusions and relevanceUsing a translational DTI approach, comparable white matter alterations were found in patients with AUD and rats with long-term alcohol consumption. In humans and rats, a progression of DTI alterations into early abstinence (2-6 weeks) suggests an underlying process that evolves soon after cessation of alcohol use.

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Impaired response inhibition in the rat 5 choice continuous performance task during protracted abstinence from chronic alcohol consumption.

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Impaired response inhibition in the rat 5 choice continuous performance task during protracted abstinence from chronic alcohol consumption.

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