Sökning: WFRF:(Treutlein J.) >
A gene-by-sex inter...
A gene-by-sex interaction for nicotine reward: evidence from humanized mice and epidemiology
-
Bernardi, R. E. (författare)
-
Zohsel, K. (författare)
-
Hirth, N. (författare)
-
visa fler...
-
Treutlein, J. (författare)
-
Heilig, Markus (författare)
-
Laucht, M. (författare)
-
Spanagel, R. (författare)
-
Sommer, W. H. (författare)
-
visa färre...
-
(utgivare)
-
(utgivare)
- NATURE PUBLISHING GROUP 2016
- 2016
- Engelska.
-
Ingår i: Translational Psychiatry. - 2158-3188. ; 6:e861
Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- Medical and Health Sciences (hsv)
- Basic Medicine (hsv)
- Neurosciences (hsv)
- Medicin och hälsovetenskap (hsv)
- Medicinska grundvetenskaper (hsv)
- Neurovetenskaper (hsv)
Hitta via bibliotek
Till lärosätets databas