Nicotine and Pavlovian Bias

Study Overview
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Brief Summary
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Nicotine remains a major cause of health problems in the US and around the world. Insight into the behavioral changes induced by nicotine use may help advance the understanding of the mechanisms underlying the maintenance of nicotine addiction and thus the important factors involved in the quitting process. Pavlovian bias is a phenomenon that includes an approach tendency toward rewarding cues and an action withdrawal tendency in response to punishments. This phenomenon may be particularly relevant to nicotine users. The current study will use an experimental, within-subjects, repeated-measured design to investigate whether acute nicotine administration influences individual Pavlovian bias in nicotine users. By recruiting participants from the University of Southern California (USC) community and contacting participants of previous nicotine-related studies of the Addiction and Self-Control Laboratory at USC, the investigators will enroll forty adult nicotine users in the study. Participants will come to the lab twice after a 10-hour nicotine fast. At each lab visit, participants will undergo a vaping session prior to completing the study tasks. The content of the e-liquid in the vape will vary by nicotine content: the vape will either contain nicotine or not. Subsequent to vaping, participants will complete a version of the Go/No-Go task which will measure their individual levels of Pavlovian bias. The investigators will compare performance on the task across the two conditions within each participant: on- and off- nicotine, after controlling for nicotine withdrawal and nicotine tolerance. Based on past research on nicotine, the researchers anticipate that acute nicotine administration will be associated with higher levels of Pavlovian bias, compared to the off-nicotine condition. Specifically, two patterns are expected to arise: a higher likelihood of making a go-response in the win reward condition and a higher likelihood of making a no-go response in the avoid losing condition, regardless of whether it is a go or no-go trial. Participants will also complete a measure of their working memory capacity. The investigators will conduct exploratory analyses for the relationship between different nicotine conditions and working memory capacity.

Detailed Description
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Nicotine remains a major cause of health problems in the US and around the world. Insight into the behavioral changes induced by nicotine use may help advance the understanding of the mechanisms underlying the maintenance of nicotine addiction and thus the important factors involved in the quitting process. Pavlovian bias is a phenomenon that includes an approach tendency toward rewarding cues and a tendency to withdraw from action in response to punishments. This phenomenon may be particularly relevant in the context of addiction and impulsive behavior patterns. The current project proposes to examine Pavlovian bias in the context of nicotine use. Specifically, the study aims to explore whether acute nicotine administration affects Pavlovian bias among nicotine users. Previous studies suggest that Pavlovian bias is a universal phenomenon, but that some individuals are better at overcoming it. Nicotine has been shown to make individuals more sensitive to cues that predict loss and reward. Therefore, it is hypothesized that nicotine will increase individuals' existing Pavlovian bias levels. Moreover, understanding whether nicotine indeed does impact Pavlovian bias may provide insight into ways in which this bias affects nicotine addiction. For example, nicotine use commonly coexists with other substance use behaviors. If nicotine acutely increases Pavlovian bias, this mechanism could partially explain the general increase of impulsive behaviors among nicotine users. Purpose/Objectives/Aims/Research Questions The primary aim is to explore the effects of acute nicotine administration on Pavlovian bias. After showing eligibility to take part in the study, participants will come to the lab twice, each after a (self-reported) 10-hour abstinence from nicotine. After completing assessments of nicotine withdrawal and nicotine tolerance, participants will complete a standardized vaping bout, either with a vape with nicotine (on-nicotine) or a denicotinized one (off-nicotine). Although the exact dose of inhaled nicotine depends on the particular puff topography of participants, the standardized vape protocol is designed to deliver approximately 2mg of nicotine. Participants will be encouraged to stop if they feel they are on the verge of having any negative nicotine response (e.g., feeling some nausea). Pavlovian bias will then be assessed via performance on a version of the Go/No-Go task. Specifically, the investigators will record participants' response accuracy on each of the four trials: go-to-win-reward, no-go-to-win-reward, go-to-avoid-losing, and no-go-to-avoid-losing. Finally, participants will complete a measure of their working memory capacity. The researchers will compare performance on the task across the two conditions within each participant: on- and off- nicotine, after controlling for nicotine withdrawal and nicotine tolerance. The investigators will also conduct exploratory analyses to determine whether participants' working memory capacity is affected by the different nicotine conditions. Aim: Examine the effects of acute nicotine administration on Pavlovian bias. The investigators will explore the effects of acute nicotine on go-bias and no-go bias. They anticipate that some level of Pavlovian bias will be observed across both sessions, on- and off- nicotine. Two patterns are expected to arise: a higher likelihood of making a go-response in the win reward condition and a higher likelihood of making a no-go response in the avoid losing condition, regardless of whether it is a go or no-go trial. However, after acute nicotine administration, participants will exhibit higher levels of Pavlovian bias, compared to the off-nicotine condition. Understanding whether nicotine indeed does impact Pavlovian bias may provide insight into ways in which this bias affects nicotine addiction.

Official Title
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Effects of Acute Nicotine Administration on Motivational Mechanisms

Conditions
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Nicotine Vaping, Nicotine Dependence

Intervention / Treatment
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* Drug: Nicotine
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 21 years old Current nicotine user (at least monthly use over the past 3 months) Reported willingness to abstain from all nicotine for at least 10 hours prior to the two lab visits English Language Competency Exclusion Criteria: - Currently pregnant, planning to become pregnant, or breastfeeding

Ages Eligible for Study
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Minimum Age: 21 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: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The participant will be randomized to receive either the regular vape with nicotine or the placebo nicotine vape first and will complete a standardized vaping session with the assigned vape. Each participant will receive both vape conditions, one at each laboratory visit. Moreover, they will not know the order of administration. After completing the vaping session, participants will be instructed on how to complete a version of the Go/No-Go task. They will see geometrical shapes on the screen, each of which will signal a particular trial type: go-win-win-reward, no-go-to-win-reward, go-to-avoid-losing, or no-go-to-avoid-losing. Participants will be explicitly instructed that the color of the cue edge will correspond to a specific trial: green will represent a win reward condition and red will represent an avoid losing condition.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nicotine<br>Participants will follow a standard vape protocol designed to deliver the approximate nicotine typically consumed from 1 cigarette (1.25 mg) | Drug: Nicotine<br>* Nicotine delivered through a vape<br>|
| Placebo Comparator: Placebo<br>Participants will follow a standard vape protocol that is equal inhalation to that used in the nicotine condition. | Other: Placebo<br>* Placebo nicotine-free vaping liquid delivered through a vape<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Levels of Pavlovian Bias measured through a version of the Go/No-Go task | Participants will complete a version of the Go/No-Go task, which allows to measure individual levels of Pavlovian bias. Pavlovian bias is a phenomenon that includes an approach tendency toward rewarding cues and a tendency to withdraw from action in response to punishments. In the task, participants choose a response (go or no-go) for various visual cues which have specific response-dependent outcomes.The Go/No-Go task design allows to collect participants' task accuracy scores (task accuracy will signify how many correct cue-dependent responses participants make). | 0 hours after using the vaping device (right after) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nicotine