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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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.

Conditions
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Tobacco Use Disorder

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Healthy smokers<br>Healthy male and female smokers. Each subject will undergo PET scan (along with craving and anxiety questionnaires) on two conditions - Smoking and Non-smoking - on two separate visits. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| [11C]-(+)-PHNO binding potential | The process of imaging requires the injection of a positron-emitting radiotracer (here, [11C]-(+)-PHNO) that binds to the protein of interest (here, dopamine receptor DRD2/3) followed by the measurement of this binding using the PET scanner. Dopamine release increases DRD 2/3 occcupancy which results in decreased radiotracer's binding potential, and vice versa. [11C]-(+)-PHNO binding potential will be measured on two different conditions (Smoking vs. Non-smoking) on two separate days. | Up to 14 days between PET scans | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjective reports of craving | Levels of subjective craving will be assessed prior to and after each condition (Smoking vs. Non-smoking) on two separate days. Minnesota Nicotine Withdrawal Scale, Tiffany Questionnaire of Smoking Urges, The Urge to Smoke scale, Tobacco Craving Questionnaire, and 21-item Visual Analogue Scale will be used. | Up to 14 days between PET scans | 
| Subjective reports of anxiety | Subjective reports of anxiety will be collected prior to and after each condition (Smoking vs. Non-smoking) on two separate days. State anxiety questions from the Spielberg State-Trait Anxiety Inventory will be used. | Up to 14 days between PET scans | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Smoking-induced dopamine release, [11C]-(+)-PHNO PET Study