Quantitation of Human Cerebral Nicotinie Receptors With 2[18F]FA-85380 and PET Healthy Non-smokers and Ex-Smokers and in Heavy and Light Situational Smokers

• Age: Subjects will be male and female volunteers aged 18 to 50 years.
• All subjects must have a stable point of contact and must agree to participate in three PET studies at approximately 4-week intervals.
• All participants in the light or heavy smoker groups must have smoking experience. Those in the heavy smoker group must smoke at least 15 cigarettes/day and have smoked for at least the last 2 consecutive years. Those participants in the light smoker group should be situational smokers (those who often smoke while consuming alcohol or in another type of situation, but who do not smoke daily). Light smokers should have not smoked more than 1 cigarette in the week before starting the medical screening process and agree to not smoke for the week before the first PET study (except for the single cigarette we ask them to smoke). Participants in the heavy smoker group should have experience with abstaining from smoking for at least 48 h. Subjects in the control group must be nonsmokers or have ceased smoking at least two years before the start of the study.

EXCLUSION CRITERIA:

• Weight: Anyone weighing more than 300 lbs is excluded from the study.
• Psychiatric disease: DSM-IV criteria will be used (American Psychiatric Association, 1994). No subject with a current axis I diagnosis will be allowed. No subject with known claustrophobia will be allowed.
• History of Drug Abuse: Volunteers reporting current or having a significant history of illicit drug abuse (single illicit substance use of more than 30 times in a lifetime for any given substance, except marijuana) will be excluded from the study. However, if the use was greater than 10 times in a lifetime, it must have occurred more than 10 years before enrollment in this protocol. Subjects may use moderate amounts of alcohol and caffeine and smoke an occasional marijuana cigarette. Moderate alcohol use will be defined as less than fourteen drinks of liquor (1.5 oz) or the equivalent beer (12 oz) or wine (5 oz) per week. Moderate caffeine use will be defined as less than 500 mg of caffeine per day, where 100 mg is equivalent to 1 serving of coffee (5 oz serving), 2.5 servings (12 oz serving) of caffeinated soft drinks, or 2.5 servings of tea (5 oz serving). Occasional marijuana use will be defined as less than or equal to two marijuana cigarettes/month.
• Current Medication Use: Volunteers may not currently use chronic (daily or for more than 10/14 days in the last month) prescription or over the counter medications, (including, but not limited to, anti-hypertensive, anti-allergy, pain).
• 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.
• Cardiovascular, pulmonary, or systemic disease: Repeated (measured on three separate occasions) diastolic blood pressure > 90 mm Hg, or systolic blood pressure > 150 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, type I diabetes mellitus, current gastrointestinal disease, gastritis or ulcers.
• Special considerations for female subjects. Female participants who are currently pregnant or nursing will not be allowed to participate in this study because of potential damage to the fetus or baby from the radiation. Female subjects will be given a serum pregnancy test (quantitative beta HCG) within 24 hours of each PET study.
• Radiation exposure: Any subject who has participated in any research studies in which he/she received a radiation exposure that would result in combination with the present study, in a total effective radiation exposure (from research studies) exceeding 3.0 rem in a 13-week period or 5.0 rem in a year.
• Lack of bilateral arterial patency: Evidence of inadequate patency of radial and lunar arteries, determined by either Doppler flow measurements or a positive Allen's test, is an exclusionary criterion for insertion of an arterial catheter.
• Women who are pregnant or lactating and children under the age of 18 will be excluded to avoid unnecessary exposure to radiation to these populations.
• Presence in body of metallic implants or materials that could be moved by the magnet of the MRI scanner: pacemakers, surgical implants, aneurysm clips, dental braces, bullet(s) or other metallic materials.
• Miscellaneous exclusionary criteria: Body mass index less than 19 or greater than 30. Hematocrit \< 39.0 for males or \< 36.0 for females.
• Novocain allergy.