The Effects of Ketamine and Guanfacine on Working Memory in Healthy Subjects (GuaKet)

Inclusion Criteria:

• Age between 21 and 45, inclusive
• Right-handed
• Have at least a 12th grade education level or equivalent
• Able to read and write English as a primary language
• Willing to refrain from caffeine and alcohol use for one week prior to each MRI session.

Exclusion Criteria:

• Abnormality on physical examination
• A 12 lead ECG at screening has clinically significant abnormalities as determined by the physician reading the ECG
• A positive pre-study urine drug screen or, at the study physicians' discretion on any drug screens given before the scans
• Abnormality on clinical chemistry or hematology examination at the pre-study medical screening.
• History of positive HIV or Hepatitis B.
• Has received either prescribed or over-the-counter (OTC) centrally active medicine or herbal supplements within the week prior to the MRI scan.
• History of any substance abuse disorder meeting DSM-IV criteria with the exception of nicotine
• Any history of DSM-IV Axis I psychiatric disorders,
• Any history of major medical or neurological disorders
• Any history indicating learning disability, mental retardation, or attention deficit disorder.
• First-degree relative with Axis I DSM-IV disorder including substance abuse or dependence.
• Any clinically significant abnormalities on screening electrocardiogram
• Any history of head injury
• Any evidence of psychosis-like symptoms, as indicated by elevated scores on the Perceptual Aberration-Magical Ideation (Chapman, Chapman et al. 1978; Eckblad, Chapman et al. 1983) and the revised Social Anhedonia scales(Eckblad, Chapman et al. unpublished)
• A positive urine toxicology screen for illicit substance use or positive alcohol breathalyzer test conducted at screening interview and prior to each MRI session
• Known sensitivity to ketamine.
• Body circumference of 52 inches or greater.
• History of claustrophobia
• Any clinically significant impairment of color vision or visual acuity after correction available in the scanner.
• Presence of cardiac pacemaker or other electronic device or ferromagnetic metal foreign bodies in vulnerable positions as assessed by a standard pre-MRI screening questionnaire
• Pregnancy or breast-feeding would exclude potential participants and all female subjects will receive a urine pregnancy test at screening and before each MRI scan.
• Donation of blood in excess of 500 mL within 56 days prior to dosing.
• History of sensitivity to heparin or heparin-induced thrombocytopenia.
• Blood pressure must be higher than 90/70. Pulse must be greater than 40 unless the participant is cleared by a study physician