Dissociating the role of prefrontal noradrenaline signaling in cost-benefit decision making and impulsive action
department or school: Medicine, Faculty of
data provider: DSpace
degree campus: UBCV
creator: Chernoff, Chloe
issued: 2023-04-19T17:58:13Z
issued: 2023
related degree: Master of Science - MSc
degree grantor: University of British Columbia
description: Win-paired stimuli can promote risk taking on experimental gambling paradigms in both rats and humans. We previously demonstrated that atomoxetine, a noradrenaline reuptake inhibitor, and guanfacine, a selective α2A adrenergic receptor agonist, reduced risky choice on the cued rat gambling task (crGT), a rodent decision making task in which wins are accompanied by salient audiovisual cues. Both compounds also decreased impulsive premature responding. However, the central mechanisms behind noradrenergic regulation of cue-guided risk taking and impulsivity have not yet been elucidated. Areas of the prefrontal cortex such as the lateral orbitofrontal cortex (lOFC) and prelimbic (PrL) subregion of the medial prefrontal cortex receive dense noradrenergic innervation and are highly implicated in risk assessment, action selection and impulse control. I therefore probed the prefrontal substrates of noradrenaline’s influence over gambling-like behaviour by infusing atomoxetine and guanfacine directly into either the lOFC or PrL prior to task performance. Atomoxetine infused into the lOFC improved decision making score in male rats but did not alter decision making in females. Atomoxetine also improved impulse control when infused into the PrL, yet only in risk preferring animals. Contrastingly, intra-PrL guanfacine exacerbated motor impulsivity in all subjects. Our data reveal a double dissociation such that lOFC noradrenaline importantly guides decision making, at least in males, while PrL noradrenaline signaling regulates motor impulsivity. We also show that noradrenergic manipulations differentially influence behaviour depending on baseline risk preference, suggesting that the noradrenaline system may function differently in subjects that are susceptible to the risk-promoting lure of win cues.
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/84332
note: DISSOCIATING THE ROLE OF PREFRONTAL NORADRENALINE SIGNALING IN COST-BENEFIT DECISION MAKING AND IMPULSIVE ACTION by Chloe Chernoff B.Sc., The University of British Columbia, 2021 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Neuroscience) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) April 2023 © Chloe Chernoff, 2023 ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the thesis entitled: Dissociating the role of prefrontal noradrenaline signaling in cost-benefit decision making and impulsive action submitted by Chloe Chernoff in partial fulfilment of the requirements for the degree of Master of Science in Neuroscience Examining Committee: Dr. Catharine Winstanley, Professor, Department of Psychology, UBC Supervisor Dr. Stan Floresco, Professor, Department of Psychology, UBC Supervisory Committee Member Dr. Mark Cembrowski, Professor, Department of Cellular and Physiological Sciences, UBC Supervisory Committee Member Dr. Tim Murphy, Professor, Department of Psychiatry, UBC Additional Examiner iii Abstract Win-paired stimuli can promote risk taking on experimental gambling paradigms in both rats and humans. We previously demonstrated that atomoxetine, a noradrenaline reuptake inhibitor, and guanfacine, a selective α2A adrenergic receptor agonist, reduced risky choice on the cued rat gambling task (crGT), a rodent decision making task in which wins are accompanied by salient audiovisual cues. Both compounds also decreased impulsive premature responding. However, the central mechanisms behind noradrenergic regulation of cue-guided risk taking and impulsivity have not yet been elucidated. Areas of the prefrontal cortex such as the lateral orbitofrontal cortex (lOFC) and prelimbic (PrL) subregion of the medial prefrontal cortex receive dense noradrenergic innervation and are highl…
has type: Thesis/Dissertation
date issued: 2023-05
is shown at: 10.14288/1.0431176
language: eng
degree discipline: Neuroscience
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
contributor: Winstanley, Catharine
type: Text
identifier URI: http://hdl.handle.net/2429/84332