Imaging Extrastriatal Dopamine Release in Tobacco Smokers and Nonsmokers

Aim 1:

To determine sex differences in amphetamine-induced dopamine (DA) release in healthy tobacco smokers and nonsmokers.

FLB-457 has been used in several PET centers and has recently been approved for use at the Yale University PET Center. We would like to determine whether there are sex differences in amphetamine induced DA release in healthy tobacco smokers and nonsmokers. Specifically, 40 healthy tobacco smokers and 40 healthy nonsmokers will have an magnetic resonance imaging (MRI) scan followed on another day by two FLB scans (ideally, the two PET scans will be carried out in the same day). Starting at 3 hours before the second PET scan, amphetamine (0.4mg/kg, PO) will be administered.

Aim 2:

To determine sex differences in amphetamine-induced dopamine release in tobacco smokers from Aim 1 after treatment with guanfacine. Guanfacine will be given under a different protocol. We plan to determine whether guanfacine treatment differentially inhibits amphetamine-induced DA release in men and smokers from Aim 1. After their first scan, the same 40 healthy tobacco smokers from Aim 1 will take guanfacine for 3 weeks under and then will have another set of FLB scans (ideally, the two PET scans will be carried out in the same day). Starting at 3 hours before the second PET scan, amphetamine (0.4mg/kg, PO) will be administered, as before. The sets of scans will be separated by at least 21 days, but due to scheduling and technical difficulties the second set may be scheduled up to 6 weeks after the first set.