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Suppression of corticostriatal circuit activity improves cognitive flexibility and prevents body weight loss in activity-based anorexia in rats
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Milton, Laura K., Mirabella, Paul N., Greaves, Erika, Spanswick, David, van den Buuse, Maarten, Oldfield, Brian J. and Foldi, Claire J. (2021) Suppression of corticostriatal circuit activity improves cognitive flexibility and prevents body weight loss in activity-based anorexia in rats. Biological Psychiatry, 90 (12). pp. 819-828. doi:10.1016/j.biopsych.2020.06.022 ISSN 00063223.
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Official URL: https://doi.org/10.1016/j.biopsych.2020.06.022
Abstract
Background
The ability to adapt behavior to changing environmental circumstances, or cognitive flexibility, is impaired in multiple psychiatric conditions, including anorexia nervosa (AN). Exaggerated prefrontal cortical activity likely underpins the inflexible thinking and rigid behaviors exhibited by patients with AN. A better understanding of the neural basis of cognitive flexibility is necessary to enable treatment approaches that may target impaired executive control.
Methods
Utilizing the activity-based anorexia (ABA) model and touchscreen operant learning paradigms, we investigated the neurobiological link between pathological weight loss and cognitive flexibility. We used pathway-specific chemogenetics to selectively modulate activity in neurons of the medial prefrontal cortex (mPFC) projecting to the nucleus accumbens shell (AcbSh) in female Sprague Dawley rats.
Result
DREADD (designer receptor exclusively activated by designer drugs)-based inhibition of the mPFC-AcbSh pathway prevented weight loss in ABA and improved flexibility during early reversal learning by reducing perseverative responding. Modulation of activity within the mPFC-AcbSh pathway had no effect on running, locomotor activity, or feeding under ad libitum conditions, indicating the specific involvement of this circuit in conditions of dysregulated reward.
Conclusions
Parallel attenuation of weight loss in ABA and improvement of cognitive flexibility following suppression of mPFC-AcbSh activity align with the relationship between disrupted prefrontal function and cognitive rigidity in AN patients. The identification of a neurobiological correlate between cognitive flexibility and pathological weight loss provides a unique insight into the executive control of feeding behavior. It also highlights the utility of the ABA model for understanding the biological bases of cognitive deficits in AN and provides context for new treatment strategies.
Item Type: | Journal Article | ||||||||
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Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School | ||||||||
SWORD Depositor: | Library Publications Router | ||||||||
Journal or Publication Title: | Biological Psychiatry | ||||||||
Publisher: | Elsevier | ||||||||
ISSN: | 00063223 | ||||||||
Official Date: | 15 November 2021 | ||||||||
Dates: |
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Volume: | 90 | ||||||||
Number: | 12 | ||||||||
Page Range: | pp. 819-828 | ||||||||
DOI: | 10.1016/j.biopsych.2020.06.022 | ||||||||
Status: | Peer Reviewed | ||||||||
Publication Status: | Published | ||||||||
Reuse Statement (publisher, data, author rights): | ** Article version: AM ** Embargo end date: 15-11-2022 ** From Elsevier via Jisc Publications Router ** History: accepted 22-06-2020; epub 15-11-2021; issued 15-12-2021. ** Licence for AM version of this article starting on 15-11-2022: http://creativecommons.org/licenses/by-nc-nd/4.0/ | ||||||||
Access rights to Published version: | Restricted or Subscription Access |
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