Acute and Chronic Nicotine Modulation of Reinforcement Learning (NicLearning)

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.

Study Overview

• Status: Completed
• Conditions: Nicotine Addiction
• Intervention / Treatment: Drug: Nicotine polacrilex; Drug: Placebo; Other: satiety; Other: abstinence

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Merideth A Addicott, PhD, Duke University

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Actual): August 31, 2016
• Study Completion (Actual): August 31, 2016

Study Registration Dates

• First Submitted: April 10, 2013
• First Submitted That Met QC Criteria: April 10, 2013
• First Posted (Estimate): April 12, 2013

Study Record Updates

• Last Update Posted (Actual): December 19, 2017
• Last Update Submitted That Met QC Criteria: November 17, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: Smoking; fMRI; Cigarettes; Nicotine; Reinforcement Learning
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Tobacco Use Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine
• Other Study ID Numbers: Pro00043890