Reward Emotion Learning and Ketamine Study

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.


Eligibility Criteria:
Inclusion Criteria:

* BMI between 18 and 30
* Participant is willing and able to give informed consent for participation in the study
* Sufficient knowledge of English language to understand and complete study tasks
* Willingness to refrain from driving, cycling, or operating heavy machinery, until the following morning or a restful sleep has occurred, whichever is later.
* Willingness to refrain from signing legal documents within 7 days after the infusion visit.
* Willingness to refrain from drinking alcohol for 3 days before the infusion visit and one day before any of the other visits throughout the study

Exclusion Criteria:

* Any current or past DSM-V significant psychiatric disorder including any psychotic, mood and anxiety and borderline personality disorders
* History of, or current medical conditions which in the opinion of the investigator may interfere with the safety of the participant or the scientific integrity of the study, including epilepsy/seizures, brain injury, hepatic or renal disease, severe gastro-intestinal problems, Central Nervous System (CNS) tumours, neurological conditions
* First-degree relative with a diagnosis of schizophrenia-spectrum or other psychotic disorder, or bipolar disorder
* History of unexplained hallucinations or impulse control problems (e.g. pathological gambling)
* Current or past history of heart rhythm disorders
* Clinically significant hypertension
* Increased intraocular pressure/glaucoma
* Current pregnancy (as determined by urine pregnancy test taken during Screening and Infusion Visits) or breastfeeding
* Clinically significant abnormal values for clinical chemistry (e.g. liver function tests), urine drug screen, blood pressure measurement and ECG. A participant with a clinical abnormality or parameters outside the reference range for the population being studied may be included only if the Investigator considers that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures
* Current or previous intake (last three months) of any medication that has a significant potential to affect mental functioning (e.g. benzodiazepines, antidepressants, neuroleptics etc.)
* Any intake of recreational drugs in the last 3 months (e.g. marijuana, ecstasy etc.)
* Lifetime recreational use of ketamine or phencyclidine
* Regular alcohol consumption of more than 14 units a week or excessive alcohol consumption up to three days before any of the in-person study visits
* Inability to abstain from alcohol for more than 1 week
* Regular smoker (\> 5 cigarettes per day)
* Excessive caffeine user (\> 6 caffeinated drinks per day)
* History of recurrent rashes or history of allergic reactions to relevant substances (ketamine treatment, placebo treatment)
* Previous participation in a study using the same or similar tasks
* Current participation in another study or participation in similar study within the last 6 months
* Participant is unlikely to comply with the clinical study protocol or is unsuitable for any other reason, in the opinion of the Investigator
* Claustrophobia
* Any implants (including dental implants) or pacemaker
* Tattoos above the chest
* Any other MRI contraindications outlined in FMRIB 7 Tesla scanning safety form