Publication Date
2023
Journal or Book Title
Psychopharmacology
Abstract
Rationale
Win-paired stimuli can promote risk taking in 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 risk taking on the cued rat gambling task (crGT), a rodent assay of risky choice in which wins are accompanied by salient cues. Both compounds also decreased impulsive premature responding.
Objective
The key neural loci mediating these effects were unknown. The lateral orbitofrontal cortex (lOFC) and the medial prefrontal cortex (mPFC), which are highly implicated in risk assessment, action selection, and impulse control, receive dense noradrenergic innervation. We therefore infused atomoxetine and guanfacine directly into either the lOFC or prelimbic (PrL) mPFC prior to task performance.
Results
When infused into the lOFC, atomoxetine improved decision making score and adaptive lose-shift behaviour in males, but not in females, without altering motor impulsivity. Conversely, intra-PrL atomoxetine improved impulse control in risk preferring animals of both sexes, but did not alter decision making. Guanfacine administered into the PrL, but not lOFC, also altered motor impulsivity in all subjects, though in the opposite direction to atomoxetine.
Conclusions
These data highlight a double dissociation between the behavioural effects of noradrenergic signaling across frontal regions with respect to risky choice and impulsive action. Given that the influence of noradrenergic manipulations on motor impulsivity could depend on baseline risk preference, these data also suggest that the noradrenaline system may function differently in subjects that are susceptible to the risk-promoting lure of win-associated cues.
DOI
https://doi.org/10.1007/s00213-023-06508-2
Pages
767-783
Volume
241
License
UMass Amherst Open Access Policy
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Recommended Citation
Ramaiah, Shrishti and et. al., "Noradrenergic regulation of cue-guided decision making and impulsivity is doubly dissociable across frontal brain regions" (2023). Psychopharmacology. 65.
https://doi.org/10.1007/s00213-023-06508-2