Mar 30, 2020

Suppression of cortico-striatal circuit activity improves cognitive flexibility and prevents body weight loss in activity-based anorexia in rats

BioRxiv : the Preprint Server for Biology
Yuval ElhanatiClaire J Foldi


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) rat 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. Results: DREADD-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 o...Continue Reading

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Mentioned in this Paper

Botulinum neurotoxin A (870-1295)
V(D)J Recombination
Gene Insertion
Somatic Hypermutation of Immunoglobulin Genes
DNA Sequence
Somatic Hypermutation, Immunoglobulin

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