The study will evaluate the effects of the mGluR2/3 partial agonist LY2140023 (Pomaglumetad Methionil, "POMA") at selected doses on ketamine-stimulated glutamate release in prefrontal cortex as measured by pharmacoBOLD fMRI (also termed resting BOLD fMRI).

This study evaluates the effects of POMA at selected doses on ketamine-stimulated glutamate increase in the prefrontal cortex hypothesized to simulate the synaptic dysregulation that occurs endogenously in the pathogenesis of schizophrenia. The purpose of this is: 1) to determine whether the low dose (40 mg BID) utilized in recent (failed) clinical trials is sufficient to engage the primary target and 2) whether a higher (160 mg BID) dose, representing the maximum tolerated dose of POMA, engages the target to a greater degree. This study will further validate pharmacoBOLD as biomarker of mGluR2/3 target engagement, permitting its future use in other glutamatergic drug development.

Inclusion Criteria:

• Medically healthy
• Capable of understanding the study procedures and able to provide informed consent
• Men and women must agree to use a reliable method of birth control during the study. Women who are post-menopausal or otherwise not of childbearing potential are also eligible

Exclusion Criteria:

• Current or past Axis I psychiatric history
• Positive urine toxicology
• History of recreational ketamine use, recreational PCP use, or an adverse reaction to ketamine. Subjects who have participated in prior research ketamine studies will be eligible. Subjects can have infusions not more frequently than biweekly, and not more than 1/month on average, therefore subjects entering the study will need to wait one month if they had a single infusion and 6 weeks if they have had two closely spaced infusions.
• History of first-degree relative with schizophrenia
• History of violence
• Presence or positive history of significant medical illness
• Presence or positive history neurological illness or any other disease/procedure/accident/intervention association with significant injury to or malfunction of the central nervous system (CNS) or history of significant head injury
• Pregnancy or breast feeding
• Metal implants, pacemaker, other metal or paramagnetic objects contained within the body
• Medicinal patch, unless removed prior to MRI scan
• Currently taking any psychotropic medication, including antidepressant medications, benzodiazepines, antipsychotic medications, mood stabilizers, anti-epileptic medications and stimulants.
• Claustrophobia
• Suicidal ideation with intent or plan in the 6 months prior to screening
• Weight > 86.95 kg (191.2 lbs)
• Subthreshold pharmacoBOLD response during screening ketamine infusion

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