Loading...
Ketamine modulates the neural correlates of reward processing in unmedicated patients in remission from depression
Kotoula, Vasileia Stringaris, Argyris Mackes, Nuria Mazibuko, Ndabezinhle Hawkins, Peter C. T. Furey, Maura Curran, H. Valerie Mehta, Mitul A.
Kotoula, Vasileia
Stringaris, Argyris
Mackes, Nuria
Mazibuko, Ndabezinhle
Hawkins, Peter C. T.
Furey, Maura
Curran, H. Valerie
Mehta, Mitul A.
Abstract
Background: Ketamine as an antidepressant improves anhedonia as early as 2 hours after infusion. These drug effects are thought to be exerted via actions on reward-related brain areas—yet these actions remain largely unknown. Our study investigates ketamine’s effects during the anticipation and receipt of an expected reward, after the psychotomimetic effects of ketamine have passed, when early antidepressant effects are reported.
Methods: We examined ketamine’s effects during the anticipation and receipt of expected rewards on predefined brain areas, namely, the dorsal and ventral striatum, ventral tegmental area, amygdala, and insula. We recruited 37 male and female participants with remitted depression who were free from symptoms and antidepressant treatments at the time of the scan. Participants were scanned 2 hours after drug administration in a double-blind crossover design (ketamine: 0.5 mg/kg and placebo) while performing a monetary reward task.
Results: A significant main effect of ketamine was observed across all regions of interest during the anticipation and feedback phases of win and no-win trials. The drug effects were particularly prominent in the nucleus accumbens and putamen, which showed increased activation on the receipt of smaller rewards compared with neutral. The levels of (2R,6R)-hydroxynorketamine 2 hours after infusion significantly correlated with the activation observed in the ventral tegmental area for that contrast.
Conclusions: These findings demonstrate that ketamine can produce detectable changes in reward-related brain areas 2 hours after infusion, which occur without symptom changes and support the idea that ketamine might improve reward-related symptoms via modulation of response to feedback.
Keywords
(2R,6R)-HNK, feedback, ketamine, monetary incentive delay (MID), reward-processing, VTA
Date
2022
Type
Journal article
Journal
Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
Book
Volume
7
Issue
3
Page Range
285-292
Article Number
ACU Department
School of Behavioural and Health Sciences
Faculty of Health Sciences
Faculty of Health Sciences
Relation URI
Source URL
Event URL
Open Access Status
Published as ‘gold’ (paid) open access
License
CC BY 4.0
File Access
Open
Notes
© 2021 Society of Biological Psychiatry. Published by Elsevier Inc.
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).