Smoking-induced Dopamine Release: a [11C]-(+)-PHNO PET Study in Humans

Does the Insula Control Smoking-induced Dopamine Release? A TMS/[11C]-PHNO Study in Humans. Part I: Smoking-induced Dopamine Release: a [11C]-(+)-PHNO PET Study in Humans.

This study will evaluate effects of smoking on the dopaminergic system by using PET tomography with new radioligand, [11C]-(+)-PHNO. Our primary hypothesis is that smoking a cigarette will produce dopamine release and this release can be measured using PET imaging and the [11C]-(+)-PHNO radiotracer. The secondary hypothesis is that this smoking induced dopamine release will be correlated with subjective craving and anxiety ratings.

This will be a within-subjects study in healthy male and female smokers. There will be one within factor condition: Smoking and Non Smoking. Therefore, there will be a repeated measure of PET scans using [11C]-(+)-PHNO under two different conditions. Ten subjects (n=5 male and n=5 female) included in the study will come on two different days and will have a Smoking or Non smoking session performed just before the PET study. Subjective assessments will be conducted at each experimental condition.

Inclusion Criteria:

• Adult males or females
• Regular smoking of at least 10 cigarettes, excluding ultra-low nicotine cigarettes, per day for at least two years
• Score on the Fagerstrom Test for Nicotine Dependence of 4 or more
• No intention to quit or reduce tobacco use, and no treatment for tobacco dependence currently
• No history of abuse of or dependence on any other drug, defined by DSM-IV criteria

Exclusion Criteria:

• Pregnancy
• Presence of metal objects in the body or implanted electronic devices, that preclude safe MR scanning
• Claustrophobia
• Cardiovascular or cerebrovascular diseases
• Major psychiatric disorders including mood, anxiety or psychotic disorders
• History of or current neurological illnesses including seizure disorders, migraine, multiple sclerosis, movement disorders, head trauma, CVA or CNS tumor
• Gross structural brain abnormalities as revealed by T1 weighted images
• Current use or use during the previous month of medication that may affect the CNS (e.g. neuroleptics, bupropion)
• Learning disability, amnesia or other conditions that impede memory and attention