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

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 unpublished) * A positive urine toxicology screen for illicit substance use or positive alcohol breathalyzer test conducted at screening interview and prior to each MRI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