The influence of conditioned stimuli on [11C]-(+)-PHNO PET binding in tobacco smokers after a one week abstinence

Patricia Di Ciano,Sylvain Houle,Bernard Le Foll,Esmaeil Mansouri,Harriet De Wit,Isabelle Boileau

doi:10.1038/s41598-021-90915-y

Abstract

Stimuli previously paired with drugs of dependence can produce cravings that are associated with increased dopamine (DA) levels in limbic and striatal brain areas. Positron Emission Tomography (PET) imaging with [11C]-(+)-PHNO allows for a sensitive measurement of changes in DA levels. The purpose of the present study was to investigate changes in DA levels, measured with PET imaging with [11C]-(+)-PHNO, in regions of interest in smokers who had maintained abstinence for 7–10 days. Participants (N = 10) underwent two PET scans on separate days, during which they viewed either smoking-related or neutral images, in counterbalanced order. Craving was measured with the 12-item Tobacco Craving Questionnaire (TCQ) and the Questionnaire on Smoking Urges-Brief (QSU-B). Compared to neutral cues, smoking cues did not increase craving. There were no changes in [11C]-(+)-PHNO binding in the cue condition compared to the neutral condition for most regions of interest (ventral pallidum, globus pallidus, limbic striatum, associative striatum, sensorimotor striatum). However, binding potential in the substantia nigra was greater in the smoking-cue condition, indicating decreased synaptic dopamine. There is a potential change of DA level occurring in midbrain following the presentation of smoking-related cues. However, this preliminary finding would need to be validated with a larger sample.

Highlights

Cues previously paired with drugs of abuse are known to have powerful effects on drug-seeking and relapse in animals[1,2]
On the day of the positron emission tomography (PET) scans, all participants screened negative for psychoactive drugs in a urine toxicology test
Analysis of differences in B PND between the smoking and neutral cue condition revealed that B PND was higher in the presence of the smoking cue in the substantia nigra (SN), corresponding to decreased DA levels in this condition

Summary

Introduction

Cues previously paired with drugs of abuse are known to have powerful effects on drug-seeking and relapse in animals[1,2]. Drug-related cues produce greater ratings of ‘craving’ as compared to neutral cues[5]. One powerful non-invasive means of measuring DA in humans is through the use of positron emission tomography (PET) using radioligands selective for DA such as [11C]raclopride. Using PET imaging, it has been shown that drug-paired cues can increase DA levels in both dependent and non-dependent stimulant users. It was shown that cues paired with amphetamine can decrease [11C]raclopride binding (increase DA) in the ventral striatum of healthy participants[12]. In dependent and non-dependent cocaine users, [11C]raclopride binding was decreased in the dorsal caudate and dorsal putamen during cue p resentation[13,14,15]. Expired carbon monoxide (CO) Time since last cigarette (days) Mass radioligand injected (μg) Corrected activity (mCi) Specific activity at time of injection (mCi/μmol)

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