University of Sussex
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Exaggerated impulsivity: a cause or a consequence of adolescent repeated ethanol withdrawal?

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posted on 2023-06-08, 19:11 authored by Sandra Sanchez-Roige
Binge alcohol drinking is a major public health concern world wide and its occurrence is rising among young adults. Using animal and human subjects, this thesis evaluates the impact of binge drinking during a time of neurodevelopment on aspects of impulse control, and studies the potential of addressing a molecular target, the µ-opioid receptor, to alleviate elevated impulsive-like behaviour. First, the nature of impulsivity is described in a review paper. We demonstrate the suitability of the Five-Choice Serial Reaction Time Task (5-CSRTT) for measuring one facet of impulsivity, waiting impulsivity, in mice. Bridging the animal and human laboratories, we developed a novel human analogue of the 5-CSRTT (paper 2). Elevated impulsive behaviour was detected in both young human binge drinkers and in an ethanol-preferring strain of mice, suggesting impulsivity to occur as a prelude to heavy alcohol use. In a second approach (paper 3), we studied the long term effects of intermittent alcohol exposure using a mouse model of adolescent binge drinking. We revealed disrupted impulsive behaviour in adulthood in two different inbred strains, which differ in baseline impulsivity and ethanol drinking patterns, indicating that impulsivity is also a consequence of ethanol exposure. In paper 4 we studied the ability of an opioid antagonist to improve top-down control of impulsive behaviour. Consilience between species and paradigms will need to be further addressed in future studies, but antagonising µ-opioid systems may aid in preventing binge drinking by facilitating inhibitory control mechanisms. Collectively, from animal and human evidence, this thesis will argue that exaggerated impulsivity may result from repeated ethanol withdrawal in adolescence as well as being a pre-existing endophenotype contributing to adolescent binge drinking. Disentangling such a relationship may help delineate new lines of intervention for at-risk individuals.


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University of Sussex

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