Psychology of Reward and Punishment: Functional and Molecular Brain Imaging and Monoaminergic Correlates

* INCLUSION CRITERIA: 1. Aged between 18 - 45 years; 2. In good health, based on history and physical examination; and 3. Right-handed (as assessed using the Edinburgh Handedness Inventory; Oldfield, 1971) All participants in the cocaine group must meet DSM-IV criteria for cocaine dependence at the time of participation. Cocaine-dependent participants must also be positive for cocaine use in their urine toxicology screen. EXCLUSION CRITERIA: Potential participants for either experimental group will be excluded from participation in this study according to the following criteria: 1. Current drug use: Subjects may smoke regular cigarettes, use moderate amounts of alcohol and caffeine, or smoke an occasional marijuana cigarette. Moderate alcohol use is defined as for men, less than ten drinks and for women less than 7 drinks of liquor (1.5 oz) or the equivalent beer (12 oz) or wine (5 oz) per week. Moderate caffeine use is defined as less than 500 mg of caffeine per day, where one 5-oz serving of coffee and 2 12-oz servings of caffeinated soft drinks or tea each contain 100 mg. Occasional marijuana use is defined as less than or equal to 2 cigarettes/month. Participants may not use alcohol or marijuana for at least 24 hours prior to scanning, but will be allowed to smoke regular cigarettes according to their normal usage pattern. Participants who do not meet these guidelines for current drug use will not be allowed to participate in this study. 2. Current or Past Medication Use: Volunteers may not currently use chronic (defined as daily for more than 10/14 days in the last month) prescription or over the counter medications that might interfere with the imaging signal (PET or MRI) or which may interact adversely with any of the substances being given in this protocol. This will include, but not be limited to, anti-hypertensive, anti-allergy, and pain medications. In addition, the use of psychotropic medications, particularly antidepressants or antipsychotic medication, will be exclusionary. Past use of antidepressant medication will be evaluated on a case by case basis; however, use of MAOI's within 14 days of AMPH administration will be exclusionary due to the possibility of precipitating hypertensive crisis. Over the counter or prescription medications may be used on an occasional basis (for example, for the treatment of self-limited conditions, such as occasional headache, musculoskeletal discomfort, allergic symptoms or pain), but medications which can interact with AMPH such as Vitamin C, L-glutamine, sodium bicarbonate, and sodium phosphate will be exclusionary. In addition, current use of over-the-counter estrogen-like compounds will be exclusionary for female participants. Subjects who have previously had significant exposure to medications that act on the DA system (antipsychotics, psychostimulants) will also be excluded from the study. 3. CNS disease: History of known structural brain abnormalities (e.g. neoplasm, subarachnoid cysts), cerebrovascular disease, infectious disease (e.g. abscess), history of head trauma (defined as documented loss of consciousness \> 5 min or injury requiring hospitalization), history of seizures as an adult, sleep apnea, or tic disorder will all be exclusionary. 4. Cardiovascular, pulmonary, or systemic disease: Repeated (measured on three separate occasions) diastolic blood pressure \> 90 mm Hg, or systolic blood pressure \> 135 mm Hg, known arrhythmia, symptomatic or known coronary artery disease; history of endocarditis, cerebral embolism, obstructive pulmonary disease, asthma, active tuberculosis, known endocrine disease (derangements in adrenal, thyroid, bone or reproductive function), known chronic renal or hepatic dysfunction, known HIV seropositive, known current autoimmune disease involving the CNS, glaucoma, allergy to amphetamine, dextroamphetamine or known hypersensitivity to sympathomimetic amines. 5. Female participants who are currently pregnant or nursing will not be allowed to participate in this study. Female subjects will be given a serum pregnancy test a maximum of 24 hours prior to each PET session and a urine pregnancy test on the day of each fMRI session. 6. Radiation exposure: Any subject who has participated in any research studies in which he/she received a radiation exposure or has been exposed to radiation for medical or other purpose , which in combination with the present study would result in a total effective radiation exposure (from research studies) exceeding 5.0 rem in a year will be excluded. 7. Children under the age of 18 will be excluded to avoid unnecessary exposure to radiation to this population. 8. Presence in body of metallic implants or materials that could be moved by the magnet of the MRI scanner will exclude participants from this study. This will include, but not be limited to, pacemakers, surgical implants, aneurysm clips, dental braces, or bullet(s). A history of working with metal with consequent possible metal fragments in the body may also result in study exclusion. 9. Miscellaneous exclusionary criteria: Body mass greater than 300 lbs. Hematocrit \< 39.0% for males or \< 35.0% for females. Participants will also be excluded if veins are inaccessible. 10. Claustrophobia will also serve as an exclusion criterion. Control Participants In addition to those criteria outlined above, potential control participants will be excluded if they meet the following criteria: 1. Current or past psychiatric illness: DSM-IV criteria will be used (DSM-IV, APA, 1994) to determine this criterion. No subject with a current axis I diagnosis will be allowed to participate. 2. History of Drug Abuse: Control volunteers reporting either current or a significant history of illicit drug abuse (defined as single illicit substance use of more than 30 times in a lifetime for any given substance, except marijuana) will be excluded from the study. 3. Positive urine toxicology screen for either amphetamines or cocaine prior to study participation. Cocaine-Dependent Subjects Candidates for the cocaine-dependent group will be excluded from the study if: 1. They are actively seeking or engaged in substance abuse treatment. 2. They are dependent on other substances except nicotine or cocaine at the time of participation.