Neural Responses and Dysphoria: Modulation by a Pharmacological Probe

Inclusion criteria

• Male or female aged 18 to 45 years, inclusive at Randomisation visit.
• Fluent English speakers.
• Beck Depression Inventory (BDI) score of 05 or ≥10 at both Screening and Randomisation visits.
• Hamilton Depression Rating Scale (HAMD)score of <24 at both Screening and Randomisation visits.
• Healthy at Screening visit as determined by a physician.
• Female participants should be surgically sterile or abstinent or, if sexually active, be practising an effective method of birth control.
• Acceptable weight as defined by body mass index (BMI) range of 18 to 30 kg/m², inclusive.
• Normotensive with sitting (5 minutes) blood pressure between the range of 100 to 140 mmHg systolic, inclusive and 60 to 90 mmHg diastolic, inclusive at Screening.
• Non smoker or light smoker (≤ 5 cigarettes per day).
• Participants must have signed the Informed Consent Form.
• Participants providing a genetic sample must have signed the DNA consent.

Exclusion criteria

• History of alcohol or substance dependence within the last 6 months.
• Consumption of large amounts of caffeinated drinks.
• Relevant history or presence upon clinical examination, of cardiac, ophthalmologic, pulmonary, endocrine (diabetes),cancer, blood disease, gastrointestinal, hepatic or renal disease or other condition.
• History or presence of significant neurological or psychiatric conditions. Exceptions to this are participants with a history of depression for the dysphoric group. Participants with generalised anxiety disorder or other anxiety disorders may be entered at the discretion of the Investigator.
• Participants who, in the opinion of the Investigator, are at risk of suicide.
• Any use of sedative hypnotics, including benzodiazepines, zolpidem or zopiclone within the last 3 months prior to Randomisation visit.
• Any use of medications for depression in the last three months prior to Randomisation visit.
• Have received prescribed medication within 14 days prior to Randomisation visit (apart from the contraceptive pill).
• Have received over-the-counter (OTC) medicine within 48 hours prior to Randomisation visit.
• Have received an experimental drug and/or used an experimental medical device within 30 days of Randomisation visit or within a period less than 5 times the drug's half life, whichever is longer.
• If female: are pregnant or are trying to get pregnant or are currently breast feeding.
• History of, or current condition of, migraine headaches or have undergone operations to the head.
• Significant hearing impairment.
• Significant visual impairment or history of ocular treatment.
• Lefthanded.
• Previous experience of the emotional test battery experimental procedures.
• Unable to comply with magnetic resonance (MR) Patient Declaration.
• Involvement in an emergency (medically emergent) situation between Screening and Randomisation visits.
• Surgery between Screening and Randomisation visits.
• Unable or unwilling to comply with study procedures.