Concurrent PET D2/D3 Receptor Imaging and fMRI Smoking Cue Reactivity in Smokers

Concurrent PET D2/D3 Receptor Imaging and fMRI Smoking Cue Reactivity in Smokers

This trial aims to determine whether dopamine D3 receptors are elevated in smokers versus nonsmokers and whether correlations exist between D3 receptor binding potential (BP) and functional MRI (fMRI) reactivity to smoking cues, which has been associated with smoking relapse vulnerability.

Neuroimaging measures of D3 BP and smoking cue fMRI reactivity will be collected concurrently in otherwise healthy nicotine-dependent smokers and age-matched nonsmokers using a 3 Tesla MRI scanner configured to conduct fMRI and Positron Emission Tomography (PET).

We will measure D3 receptor BP using radiolabeled [11C]-(+)-PHNO, which has a relatively higher affinity for D3 versus D2 receptors.

We hypothesize that D3 BP will be elevated in smokers versus nonsmokers and that in smokers, there will be a positive correlation between smoking cue fMRI reactivity and D3 BP.

Inclusion Criteria:

• competent to provide written informed consent
• Smokers: self-report of smoking 15 or more cigarettes/day for the past year, self-report of smoking first cigarette of the day within 30 minutes of awakening, meets DSM-IV criteria for Nicotine Dependence, provides expired breath carbon monoxide reading of > 10 ppm at enrollment
• Nonsmokers: self-report of consuming <100 cigarettes in their lifetime, none in the last 6 months, provides expired breath carbon monoxide reading of < 9 ppm at enrollment
• Women of childbearing potential: negative STAT serum beta-human chorionic gonadotrophin pregnancy test before scanning

Exclusion Criteria:

• pregnant or able to become pregnant and not willing to undergo blood pregnancy test
• unstable medical illness with likely hospitalization for treatment within 6 months
• life-threatening arrhythmia, cerebro-vascular or cardiovascular event within 6 months of enrollment; liver function tests elevated over 2.5x normal; CNS tumor or seizure disorder
• users of other tobacco- or nicotine-containing products (gum, patches, e-cigarettes)
• lifetime history of DSM-IV bulimia, organic mental disorder, brain injury or psychotic disorder
• 6 month history of non-nicotine substance use disorder or major depression
• history of multiple adverse drug reactions
• current use of excluded concomitant medications (smoking cessation medications)
• known history of allergic reaction to the PET ligand [11C]-PHNO, its components, or any medication