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A gene-by-sex interaction for nicotine reward: evidence from humanized mice and epidemiology
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- Bernardi, R. E. (author)
- Heidelberg University, Germany
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- Zohsel, K. (author)
- Heidelberg University, Germany
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- Hirth, N. (author)
- Heidelberg University, Germany
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- (creator_code:org_t)
- 2016-07-26
- 2016
- English.
- In: Translational Psychiatry. - : NATURE PUBLISHING GROUP. - 2158-3188. ; 6:e861
- Journal article (peer-reviewed)
Abstract
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- It has been proposed that vulnerability to nicotine addiction is moderated by variation at the mu-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_A4G (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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
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- ref (subject category)
- art (subject category)
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- Bernardi, R. E.
- Zohsel, K.
- Hirth, N.
- Treutlein, J.
- Heilig, Markus
- Laucht, M.
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- Spanagel, R.
- Sommer, W. H.
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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- and Neurosciences
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- Translational Ps ...
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- Linköping University
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