Acute and Chronic Nicotine Modulation of Reinforcement Learning

Study Overview
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Brief Summary
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The purpose of this study is to use functional magnetic resonance imaging (fMRI) to investigate the acute and chronic effects of nicotine on motivational behavior and prediction error-related neural activation. Nonsmokers (n = 24) and smokers (n = 24) will undergo fMRI scans on two separate occasions while performing a decision-making task that will elicit prediction error signals in the mesocorticolimbic pathway of the brain. Nonsmokers will be scanned once following an acute dose of nicotine and once following placebo administration. Smokers will be scanned once following smoking as usual and once following 24-hours of smoking abstinence, in order to measure the effects of nicotine withdrawal. The study team hypothesizes that acute nicotine will increase the prediction error signal in nonsmokers compared to placebo, and that nicotine withdrawal will decrease the prediction error signal in smokers compared to the normal satiated condition. Furthermore, nonsmokers (during the placebo condition) will have greater prediction error activation than smokers (during the satiated condition). The results of this study will inform whether the initiation and maintenance of smoking behavior could be facilitated by the effects of nicotine on reinforcement learning.

Official Title
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Acute and Chronic Nicotine Modulation of Reinforcement Learning

Conditions
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Nicotine Addiction

Intervention / Treatment
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* Drug: Nicotine polacrilex
* Drug: Placebo
* Other: satiety
* Other: abstinence


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion criteria for all subjects: generally healthy between the ages of 18-55 right-handed Inclusion criteria for nonsmokers: smoked < 50 cigarettes of a brand delivering ≥ 0.5 mg nicotine (FTC method) have not smoked in ≥ 6 months afternoon expired CO concentration ≤ 5 ppm and/or morning urinary NicAlert < 100 ng/ml Inclusion criteria for smokers smoke ≥ 10 cigarettes/day of a brand delivering ≥ 0.5 mg nicotine (FTC method) smoked ≥ 2 years afternoon expired CO concentrations ≥ 10 ppm and/or morning urinary NicAlert > 100 ng/ml Exclusion Criteria: inability to attend all required experimental sessions significant health problems (e.g., current and uncontrolled liver, lung, or heart problems, current or past seizure disorder, serious head trauma) lifetime diagnosis of Axis I psychiatric disorders (e.g., depression, anxiety disorder, schizophrenia) meet DSM-V criteria for past or current substance dependence other than nicotine use of psychoactive medications as indicated by self-report use of smokeless tobacco, nicotine replacement therapy, or desire to change smoking behavior while in the study positive urine drug screen for illicit drugs or positive breath alcohol concentration presence of conditions that would make MRI unsafe having vision that cannot be corrected to 20/40 among women, nursing or a positive pregnancy test inability to achieve learning criteria in training session

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Nicotine, placebo<br>Nonsmokers will be measured following a nicotine polacrilex lozenge (2mg) on one occasion and placebo on another occasion. | Drug: Nicotine polacrilex<br>* nonsmokers will be measured following nicotine administration<br>* Other names: nicotine condition;Drug: Placebo<br>* nonsmokers will be measured following placebo administration<br>* Other names: placebo condition;|
| Other: Nicotine withdrawal or satiety<br>Smokers will be measured in a normal satiated condition and following 24-hours of smoking abstinence | Other: satiety<br>* smokers will be measured in a smoking satiated condition<br>* Other names: smoking satiated condition;Other: abstinence<br>* smokers will be measured following 24-hours of smoking abstinence<br>* Other names: smoking abstinence condition;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Blood Oxygen Level Dependent (BOLD) Signal in Dorsomedial Prefrontal Cortex | The acute and chronic effects of nicotine on the blood oxygen level dependent signal will be measured using functional magnetic resonance imaging. Reward-cue related BOLD signal on an outcome expectation task. | Nonsmokers: post nicotine and post placebo. Smokers: 24 hours smoking abstinence or smoking satiety | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Reinforcement Learning, Nicotine, Smoking, Cigarettes, fMRI