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A gene-by-sex interaction for nicotine reward: evidence from humanized mice and epidemiology

It has been proposed that vulnerability to nicotine addiction is moderated by variation at the μ-opioid receptor locus (OPRM1), but results from human studies vary and prospective studies based on genotype are lacking. We have developed a humanized mouse model of the most common functional OPRM1 pol...

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Autores principales: Bernardi, R E, Zohsel, K, Hirth, N, Treutlein, J, Heilig, M, Laucht, M, Spanagel, R, Sommer, W H
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5545715/
https://www.ncbi.nlm.nih.gov/pubmed/27459726
http://dx.doi.org/10.1038/tp.2016.132
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author Bernardi, R E
Zohsel, K
Hirth, N
Treutlein, J
Heilig, M
Laucht, M
Spanagel, R
Sommer, W H
author_facet Bernardi, R E
Zohsel, K
Hirth, N
Treutlein, J
Heilig, M
Laucht, M
Spanagel, R
Sommer, W H
author_sort Bernardi, R E
collection PubMed
description It has been proposed that vulnerability to nicotine addiction is moderated by variation at the μ-opioid receptor locus (OPRM1), but results from human studies vary and prospective studies based on genotype are lacking. We have developed a humanized mouse model of the most common functional OPRM1 polymorphism rs1799971_A>G (A118G). Here we use this model system together with a cohort of German youth to examine the role of the OPRM1 A118G variation on nicotine reward. Nicotine reinforcement was examined in the humanized mouse model using i.v. self-administration. Male (n=17) and female (n=26) mice homozygous either for the major human A allele (AA) or the minor G allele (GG) underwent eight daily 2 h sessions of nicotine self-administration. Furthermore, male (n=104) and female (n=118) subjects homozygous for the A allele or carrying the G allele from the Mannheim Study of Children at Risk were evaluated for pleasurable and unpleasant experiences during their initial smoking experience. A significant sex-by-genotype effect was observed for nicotine self-administration. Male 118GG mice demonstrated higher nicotine intake than male 118AA mice, suggesting increased nicotine reinforcement. In contrast, there was no genotype effect in female mice. Human male G allele carriers reported increased pleasurable effects from their first smoking experience, as compared to male homozygous A, female G and female homozygous A allele carriers. The 118G allele appears to confer greater sensitivity to nicotine reinforcement in males, but not females.
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spelling pubmed-55457152017-08-10 A gene-by-sex interaction for nicotine reward: evidence from humanized mice and epidemiology Bernardi, R E Zohsel, K Hirth, N Treutlein, J Heilig, M Laucht, M Spanagel, R Sommer, W H Transl Psychiatry Original Article It has been proposed that vulnerability to nicotine addiction is moderated by variation at the μ-opioid receptor locus (OPRM1), but results from human studies vary and prospective studies based on genotype are lacking. We have developed a humanized mouse model of the most common functional OPRM1 polymorphism rs1799971_A>G (A118G). Here we use this model system together with a cohort of German youth to examine the role of the OPRM1 A118G variation on nicotine reward. Nicotine reinforcement was examined in the humanized mouse model using i.v. self-administration. Male (n=17) and female (n=26) mice homozygous either for the major human A allele (AA) or the minor G allele (GG) underwent eight daily 2 h sessions of nicotine self-administration. Furthermore, male (n=104) and female (n=118) subjects homozygous for the A allele or carrying the G allele from the Mannheim Study of Children at Risk were evaluated for pleasurable and unpleasant experiences during their initial smoking experience. A significant sex-by-genotype effect was observed for nicotine self-administration. Male 118GG mice demonstrated higher nicotine intake than male 118AA mice, suggesting increased nicotine reinforcement. In contrast, there was no genotype effect in female mice. Human male G allele carriers reported increased pleasurable effects from their first smoking experience, as compared to male homozygous A, female G and female homozygous A allele carriers. The 118G allele appears to confer greater sensitivity to nicotine reinforcement in males, but not females. Nature Publishing Group 2016-07 2016-07-26 /pmc/articles/PMC5545715/ /pubmed/27459726 http://dx.doi.org/10.1038/tp.2016.132 Text en Copyright © 2016 The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Original Article
Bernardi, R E
Zohsel, K
Hirth, N
Treutlein, J
Heilig, M
Laucht, M
Spanagel, R
Sommer, W H
A gene-by-sex interaction for nicotine reward: evidence from humanized mice and epidemiology
title A gene-by-sex interaction for nicotine reward: evidence from humanized mice and epidemiology
title_full A gene-by-sex interaction for nicotine reward: evidence from humanized mice and epidemiology
title_fullStr A gene-by-sex interaction for nicotine reward: evidence from humanized mice and epidemiology
title_full_unstemmed A gene-by-sex interaction for nicotine reward: evidence from humanized mice and epidemiology
title_short A gene-by-sex interaction for nicotine reward: evidence from humanized mice and epidemiology
title_sort gene-by-sex interaction for nicotine reward: evidence from humanized mice and epidemiology
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5545715/
https://www.ncbi.nlm.nih.gov/pubmed/27459726
http://dx.doi.org/10.1038/tp.2016.132
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