The CB1R rs2023239 receptor gene variant significantly affects the reinforcing effects of nicotine, but not cue reactivity, in human smokers

Abstract Introduction The cannabinoid CB1 receptor (CB1R) has been shown in preclinical studies to be involved in nicotine reinforcement and relapse‐like behavior. The common single nucleotide polymorphism (SNP) rs2023239 may code for an alternative CB1R protein, alter CB1R expression, and be involv...

Full description

Bibliographic Details
Main Authors: Chidera C. Chukwueke, William J. Kowalczyk, Marie Gendy, Richard Taylor, Rachel F. Tyndale, Bernard Le Foll, Stephen J. Heishman
Format: Article
Language:English
Published: Wiley 2021-02-01
Series:Brain and Behavior
Subjects:
Online Access:https://doi.org/10.1002/brb3.1982
_version_ 1818677093361254400
author Chidera C. Chukwueke
William J. Kowalczyk
Marie Gendy
Richard Taylor
Rachel F. Tyndale
Bernard Le Foll
Stephen J. Heishman
author_facet Chidera C. Chukwueke
William J. Kowalczyk
Marie Gendy
Richard Taylor
Rachel F. Tyndale
Bernard Le Foll
Stephen J. Heishman
author_sort Chidera C. Chukwueke
collection DOAJ
description Abstract Introduction The cannabinoid CB1 receptor (CB1R) has been shown in preclinical studies to be involved in nicotine reinforcement and relapse‐like behavior. The common single nucleotide polymorphism (SNP) rs2023239 may code for an alternative CB1R protein, alter CB1R expression, and be involved in nicotine dependence. To date, no study has explored the relationship between this SNP in CB1R and specific phenotypes of nicotine dependence. Methods The current study investigated the influence of CB1R rs2023239 in nicotine reinforcement and craving in regular cigarette smokers. Current smokers (n = 104, cigarettes per day ≥ 10) were genetically grouped (C allele group vs. No C allele group) and underwent laboratory measures of nicotine reinforcement and smoking cue‐elicited craving. Nicotine reinforcement was assessed using a forced choice paradigm, while a cue‐reactivity procedure measured cue‐elicited craving. Results These results show that smokers with the C allele variant (CC + CT genotypes) experienced a lower nicotine reinforcement effect compared to those without the C allele (TT genotype). These results were similar in both our subjective and behavioral reinforcement measures, though the subjective effects did not withstand controlling for race. There was no difference between genotype groups with respect to cue‐elicited craving, suggesting a lack of influence in cue reactivity. Conclusion Taken together, these results suggest that the variation in the CB1R (i.e., rs2023239 SNP) may play a larger role in nicotine reinforcement compared to cue reactivity. This work provides impetus to further understand the physiological mechanisms that explain how CB1Rs influence nicotine dependence phenotypes.
first_indexed 2024-12-17T08:53:53Z
format Article
id doaj.art-535a5e63f9e543188e0a9df28bc7f873
institution Directory Open Access Journal
issn 2162-3279
language English
last_indexed 2024-12-17T08:53:53Z
publishDate 2021-02-01
publisher Wiley
record_format Article
series Brain and Behavior
spelling doaj.art-535a5e63f9e543188e0a9df28bc7f8732022-12-21T21:56:01ZengWileyBrain and Behavior2162-32792021-02-01112n/an/a10.1002/brb3.1982The CB1R rs2023239 receptor gene variant significantly affects the reinforcing effects of nicotine, but not cue reactivity, in human smokersChidera C. Chukwueke0William J. Kowalczyk1Marie Gendy2Richard Taylor3Rachel F. Tyndale4Bernard Le Foll5Stephen J. Heishman6Translational Addiction Research Laboratory Centre for Addiction and Mental Health (CAMH) Toronto ON CanadaIntramural Research Program National Institute on Drug Abuse Baltimore MD USATranslational Addiction Research Laboratory Centre for Addiction and Mental Health (CAMH) Toronto ON CanadaIntramural Research Program National Institute on Drug Abuse Baltimore MD USADepartment of Pharmacology University of Toronto Toronto ON CanadaTranslational Addiction Research Laboratory Centre for Addiction and Mental Health (CAMH) Toronto ON CanadaIntramural Research Program National Institute on Drug Abuse Baltimore MD USAAbstract Introduction The cannabinoid CB1 receptor (CB1R) has been shown in preclinical studies to be involved in nicotine reinforcement and relapse‐like behavior. The common single nucleotide polymorphism (SNP) rs2023239 may code for an alternative CB1R protein, alter CB1R expression, and be involved in nicotine dependence. To date, no study has explored the relationship between this SNP in CB1R and specific phenotypes of nicotine dependence. Methods The current study investigated the influence of CB1R rs2023239 in nicotine reinforcement and craving in regular cigarette smokers. Current smokers (n = 104, cigarettes per day ≥ 10) were genetically grouped (C allele group vs. No C allele group) and underwent laboratory measures of nicotine reinforcement and smoking cue‐elicited craving. Nicotine reinforcement was assessed using a forced choice paradigm, while a cue‐reactivity procedure measured cue‐elicited craving. Results These results show that smokers with the C allele variant (CC + CT genotypes) experienced a lower nicotine reinforcement effect compared to those without the C allele (TT genotype). These results were similar in both our subjective and behavioral reinforcement measures, though the subjective effects did not withstand controlling for race. There was no difference between genotype groups with respect to cue‐elicited craving, suggesting a lack of influence in cue reactivity. Conclusion Taken together, these results suggest that the variation in the CB1R (i.e., rs2023239 SNP) may play a larger role in nicotine reinforcement compared to cue reactivity. This work provides impetus to further understand the physiological mechanisms that explain how CB1Rs influence nicotine dependence phenotypes.https://doi.org/10.1002/brb3.1982CB1Rgenotypenicotine cue reactivitynicotine dependencenicotine reinforcement
spellingShingle Chidera C. Chukwueke
William J. Kowalczyk
Marie Gendy
Richard Taylor
Rachel F. Tyndale
Bernard Le Foll
Stephen J. Heishman
The CB1R rs2023239 receptor gene variant significantly affects the reinforcing effects of nicotine, but not cue reactivity, in human smokers
Brain and Behavior
CB1R
genotype
nicotine cue reactivity
nicotine dependence
nicotine reinforcement
title The CB1R rs2023239 receptor gene variant significantly affects the reinforcing effects of nicotine, but not cue reactivity, in human smokers
title_full The CB1R rs2023239 receptor gene variant significantly affects the reinforcing effects of nicotine, but not cue reactivity, in human smokers
title_fullStr The CB1R rs2023239 receptor gene variant significantly affects the reinforcing effects of nicotine, but not cue reactivity, in human smokers
title_full_unstemmed The CB1R rs2023239 receptor gene variant significantly affects the reinforcing effects of nicotine, but not cue reactivity, in human smokers
title_short The CB1R rs2023239 receptor gene variant significantly affects the reinforcing effects of nicotine, but not cue reactivity, in human smokers
title_sort cb1r rs2023239 receptor gene variant significantly affects the reinforcing effects of nicotine but not cue reactivity in human smokers
topic CB1R
genotype
nicotine cue reactivity
nicotine dependence
nicotine reinforcement
url https://doi.org/10.1002/brb3.1982
work_keys_str_mv AT chideracchukwueke thecb1rrs2023239receptorgenevariantsignificantlyaffectsthereinforcingeffectsofnicotinebutnotcuereactivityinhumansmokers
AT williamjkowalczyk thecb1rrs2023239receptorgenevariantsignificantlyaffectsthereinforcingeffectsofnicotinebutnotcuereactivityinhumansmokers
AT mariegendy thecb1rrs2023239receptorgenevariantsignificantlyaffectsthereinforcingeffectsofnicotinebutnotcuereactivityinhumansmokers
AT richardtaylor thecb1rrs2023239receptorgenevariantsignificantlyaffectsthereinforcingeffectsofnicotinebutnotcuereactivityinhumansmokers
AT rachelftyndale thecb1rrs2023239receptorgenevariantsignificantlyaffectsthereinforcingeffectsofnicotinebutnotcuereactivityinhumansmokers
AT bernardlefoll thecb1rrs2023239receptorgenevariantsignificantlyaffectsthereinforcingeffectsofnicotinebutnotcuereactivityinhumansmokers
AT stephenjheishman thecb1rrs2023239receptorgenevariantsignificantlyaffectsthereinforcingeffectsofnicotinebutnotcuereactivityinhumansmokers
AT chideracchukwueke cb1rrs2023239receptorgenevariantsignificantlyaffectsthereinforcingeffectsofnicotinebutnotcuereactivityinhumansmokers
AT williamjkowalczyk cb1rrs2023239receptorgenevariantsignificantlyaffectsthereinforcingeffectsofnicotinebutnotcuereactivityinhumansmokers
AT mariegendy cb1rrs2023239receptorgenevariantsignificantlyaffectsthereinforcingeffectsofnicotinebutnotcuereactivityinhumansmokers
AT richardtaylor cb1rrs2023239receptorgenevariantsignificantlyaffectsthereinforcingeffectsofnicotinebutnotcuereactivityinhumansmokers
AT rachelftyndale cb1rrs2023239receptorgenevariantsignificantlyaffectsthereinforcingeffectsofnicotinebutnotcuereactivityinhumansmokers
AT bernardlefoll cb1rrs2023239receptorgenevariantsignificantlyaffectsthereinforcingeffectsofnicotinebutnotcuereactivityinhumansmokers
AT stephenjheishman cb1rrs2023239receptorgenevariantsignificantlyaffectsthereinforcingeffectsofnicotinebutnotcuereactivityinhumansmokers