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Ketamine reverses stress-induced hypersensitivity to sunk costs.

Romain Durand-De Cuttoli, Brian M Sweis

bioRxiv : the preprint server for biology May 14, 2024 preprint DOI: 10.1101/2024.05.12.593597 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Randomized controlled trial Longitudinal
Population Mice
Intervention Ketamine
Dose 20 mg/kg
Topics Esketamine Ketamine
Keywords Behavioral-economics Mental-health Decision-making Stress-management
Citations 1
Key findings Chronic social defeat stress increased sunk cost sensitivity in mice, and a single dose of ketamine normalized this hypersensitivity in stressed mice while abolishing it in non-stressed mice.

Abstract

How mood interacts with information processing in the brain is thought to mediate the maladaptive behaviors observed in depressed individuals. However, the neural mechanisms underlying impairments in emotion-cognition interactions are poorly understood. This includes influencing the balance between how past-sensitive vs. future-looking one is during decision-making. Recent insights from the field of neuroeconomics offer novel approaches to study changes in such valuation processes in a manner that is biologically tractable and readily translatable across species. We recently discovered that rodents are sensitive to "sunk costs" - a feature of higher cognition previously thought to be unique to humans. The sunk costs bias describes the phenomenon in which an individual overvalues and escalates commitment to continuing an ongoing endeavor, even if suboptimal, as a function of irrecoverable past (sunk) losses - information that, according to classic economic theory, should be ignored. In the present study, mice were exposed to chronic social defeat stress paradigm, a well-established animal model used for the study of depression. Mice were then tested on our longitudinal neuroeconomic foraging task, Restaurant Row. We found mice exposed to this severe stressor displayed an increased sensitivity to sunk costs, without altering overall willingness to wait. Mice were then randomly assigned to receive a single intraperitoneal injection of either saline or ketamine (20 mg/kg). We discovered that stress-induced hypersensitivity to sunk costs was renormalized following a single dose of ketamine. Interestingly, in non-defeated mice, ketamine treatment completely abolished sunk cost sensitivity, causing mice to no longer value irrecoverable losses during re-evaluation decisions who instead based choices solely on the future investment required to obtain a goal. These findings suggest that the antidepressant effects of ketamine may be mediated in part through changes in the processing of past-sensitive information during on-going decision-making, reducing its weight as a potential source of cognitive dissonance that could modulate behavior and instead promoting more future-thinking behavior.

Comparable studies

Other preclinical and animal studies on ketamine, most cited first.

Study Year Design Participants
mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats 2010 Observational study
Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats 1997 Dose-response study with microdialysis and behavioral testing
NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice 2016 Preclinical study
The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats 1983 Experimental study
R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice 2015 Experimental study

Citations in the library

Cites 4

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Esketamine Ketamine Depression