Acute and Chronic Nicotine Modulation of Reinforcement Learning

Acute and Chronic Nicotine Modulation of Reinforcement Learning

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.

Inclusion Criteria:

Inclusion criteria for all subjects:

1. generally healthy
2. between the ages of 18-55
3. right-handed

Inclusion criteria for nonsmokers:

1. smoked < 50 cigarettes of a brand delivering ≥ 0.5 mg nicotine (FTC method)
2. have not smoked in ≥ 6 months
3. afternoon expired CO concentration ≤ 5 ppm and/or morning urinary NicAlert < 100 ng/ml

Inclusion criteria for smokers

1. smoke ≥ 10 cigarettes/day of a brand delivering ≥ 0.5 mg nicotine (FTC method)
2. smoked ≥ 2 years
3. afternoon expired CO concentrations ≥ 10 ppm and/or morning urinary NicAlert > 100 ng/ml

Exclusion Criteria:

1. inability to attend all required experimental sessions
2. significant health problems (e.g., current and uncontrolled liver, lung, or heart problems, current or past seizure disorder, serious head trauma)
3. lifetime diagnosis of Axis I psychiatric disorders (e.g., depression, anxiety disorder, schizophrenia)
4. meet DSM-V criteria for past or current substance dependence other than nicotine
5. use of psychoactive medications as indicated by self-report
6. use of smokeless tobacco, nicotine replacement therapy, or desire to change smoking behavior while in the study
7. positive urine drug screen for illicit drugs or positive breath alcohol concentration
8. presence of conditions that would make MRI unsafe
9. having vision that cannot be corrected to 20/40
10. among women, nursing or a positive pregnancy test
11. inability to achieve learning criteria in training session