Ketamine's efficacy as an antidepressant is now well established yet the mechanisms underlying its antidepressant effect are yet to be fully described. Work in the animal literature and research in humans is suggestive of specific effects on anhedonia and memory reconsolidation. In this study the investigators will further explore the effects of ketamine on learning and memory as well as measuring the associated changes at neural level in a sample of healthy volunteers. Participants will be assigned to receive ketamine or placebo and complete a set of tasks which will allow the investigators to quantify the effect of ketamine on learning about reward and punishment and memory for learned reward associations 24 hours after ketamine infusion. This study will help the investigators to understand the basis of ketamine's antidepressant effects and aid the development of new treatments for depression.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
70
Ketamine is a high trapping NMDA receptor antagonist which has rapid and reliable antidepressant effects in patients with major depressive disorder (MDD) who have failed to respond to conventional monoaminergic agents.
Placebo injection (0.9% sodium chloride)
University of Oxford
Oxford, United Kingdom
RECRUITINGActivation of the habenula during the Pavlovian conditioning task in response to the conditioned stimulus associated with pain stimuli and in response to the receipt of shock.
Blood Oxygen Level Dependent (BOLD) signal in the habenula at the time of the shock-associated conditioned stimulus presentation and at the time of shock delivery.
Time frame: 24 hours after ketamine infusion
Habenula response to the absence of expected reward and the receipt of an unexpected loss (i.e. a negative prediction error signal) in both the reward maximisation and loss minimisation tasks.
BOLD signal in the habenula at the time of outcome presentation in both the reward maximisation and loss minimisation tasks.
Time frame: 24 hours after ketamine administration
Preference for high-reward probability shapes learned after winning money (in the Wheel of Fortune draw) during the preference test.
Proportion of choices where high-reward probability shapes are selected. This will be based on the difference between the perceived reward probability of shapes learned after the winning and losing of money (an area under the curve measure).
Time frame: +/- 24 hours after ketamine administration
Ventral striatum response to the expected reward and the omission an unexpected loss (i.e. a positive prediction error signal) in both the reward maximisation and loss minimisation tasks.
BOLD signal in the ventral striatum at the time of outcome presentation in both the reward maximisation and loss minimisation tasks.
Time frame: 24 hours after ketamine administration
Pupil dilation (measured by an eye tracker device) in response to decision values in the affective memory preference test.
Baseline corrected pupil dilation measured at the time of option presentation during each choice trial of the affective memory preference test.
Time frame: 24 hours after ketamine administration
Difference in pupil response to shapes learned after winning versus losing money.
Between groups comparison of pupil dilation in response to shapes learned after a loss and shapes learned after a win in Wheel of Fortune draw that induces experimental change in negative/positive affect.
Time frame: 24 hours after ketamine administration
Amount of money earned in the learning and memory task.
Between groups comparison of the total amount of money earned during the learning and memory task.
Time frame: Final component completed 24 hours after ketamine administration before scanning
Change in bio-behavioral measures of stress following laboratory induced stress administered.
Between groups comparison of salivary cortisol in response to Oxford Cognition Stress Task.
Time frame: 1-week after ketamine infusion
Change in bio-behavioral measures of stress following laboratory induced stress administered.
Between groups comparison of salivary alpha amylase in response to Oxford Cognition Stress Task.
Time frame: 1-week after ketamine infusion
Change in bio-behavioral measures of stress following laboratory induced stress administered.
Between groups comparison of heart rate in response to Oxford Cognition Stress Task.
Time frame: 1-week after ketamine infusion
Change in bio-behavioral measures of stress following laboratory induced stress administered.
Between groups comparison of visual analogue scale ratings in response to Oxford Cognition Stress Task.
Time frame: 1-week after ketamine infusion
Recognition of positive and negative facial expressions.
Recognition accuracy for positive and negative facial expressions
Time frame: Immediately and 24 hours after ketamine infusion
Recognition of positive and negative facial expressions.
Reaction time to recognise positive and negative facial expressions
Time frame: Immediately and 24 hours after ketamine infusion
Categorisation of emotional words.
Accuracy of categorisation for positive and negative descriptor words.
Time frame: 24 hours after ketamine infusion
Recognition of emotional words.
Reaction time to categorise positive and negative descriptor words.
Time frame: 24 hours after ketamine infusion
Recall of emotional words.
Number of words correctly (hits) and incorrectly (false alarms) recalled.
Time frame: 24 hours after ketamine infusion
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