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Addiction-related genes in gambling disorders: new insights from parallel human and pre-clinical models

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Addiction-related genes in gambling disorders: new insights from parallel human and pre-clinical models. / Lobo, D. S. S.; Aleksandrova, L.; Knight, Jo et al.
In: Molecular Psychiatry, Vol. 20, No. 8, 08.2015, p. 1002-1010.

Research output: Contribution to Journal/MagazineJournal articlepeer-review

Harvard

Lobo, DSS, Aleksandrova, L, Knight, J, Casey, DM, el-Guebaly, N, Nobrega, JN & Kennedy, JL 2015, 'Addiction-related genes in gambling disorders: new insights from parallel human and pre-clinical models', Molecular Psychiatry, vol. 20, no. 8, pp. 1002-1010. https://doi.org/10.1038/mp.2014.113

APA

Lobo, D. S. S., Aleksandrova, L., Knight, J., Casey, D. M., el-Guebaly, N., Nobrega, J. N., & Kennedy, J. L. (2015). Addiction-related genes in gambling disorders: new insights from parallel human and pre-clinical models. Molecular Psychiatry, 20(8), 1002-1010. https://doi.org/10.1038/mp.2014.113

Vancouver

Lobo DSS, Aleksandrova L, Knight J, Casey DM, el-Guebaly N, Nobrega JN et al. Addiction-related genes in gambling disorders: new insights from parallel human and pre-clinical models. Molecular Psychiatry. 2015 Aug;20(8):1002-1010. doi: 10.1038/mp.2014.113

Author

Lobo, D. S. S. ; Aleksandrova, L. ; Knight, Jo et al. / Addiction-related genes in gambling disorders : new insights from parallel human and pre-clinical models. In: Molecular Psychiatry. 2015 ; Vol. 20, No. 8. pp. 1002-1010.

Bibtex

@article{bd92699366c04faca6c83a8cdbe4e84e,
title = "Addiction-related genes in gambling disorders: new insights from parallel human and pre-clinical models",
abstract = "Neurobiological research supports the characterization of disordered gambling (DG) as a behavioral addiction. Recently, an animal model of gambling behavior was developed (rat gambling task, rGT), expanding the available tools to investigate DG neurobiology. We investigated whether rGT performance and associated risk gene expression in the rat's brain could provide cross-translational understanding of the neuromolecular mechanisms of addiction in DG. We genotyped tagSNPs (single-nucleotide polymorphisms) in 38 addiction-related genes in 400 DG and 345 non-DG subjects. Genes with P<0.1 in the human association analyses were selected to be investigated in the animal arm to determine whether their mRNA expression in rats was associated with the rat's performance on the rGT. In humans, DG was significantly associated with tagSNPs in DRD3 (rs167771) and CAMK2D (rs3815072). Our results suggest that age and gender might moderate the association between CAMK2D and DG. Moderation effects could not be investigated due to sample power. In the animal arm, only the association between rGT performance and Drd3 expression remained significant after Bonferroni correction for 59 brain regions. As male rats were used, gender effects could not be investigated. Our results corroborate previous findings reporting the involvement of DRD3 receptor in addictions. To our knowledge, the use of human genetics, pre-clinical models and gene expression as a cross-translation paradigm has not previously been attempted in the field of addictions. The cross-validation of human findings in animal models is crucial for improving the translation of basic research into clinical treatments, which could accelerate neurobiological and pharmacological investigations in addictions.",
keywords = "Adult, Animals, Behavior, Addictive, Brain, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Disease Models, Animal, Female, Gambling, Games, Experimental, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Male, Polymorphism, Single Nucleotide, RNA, Messenger, Rats, Sprague-Dawley, Receptors, Dopamine D3, Risk",
author = "Lobo, {D. S. S.} and L. Aleksandrova and Jo Knight and Casey, {D. M.} and N. el-Guebaly and Nobrega, {J. N.} and Kennedy, {J. L.}",
year = "2015",
month = aug,
doi = "10.1038/mp.2014.113",
language = "English",
volume = "20",
pages = "1002--1010",
journal = "Molecular Psychiatry",
issn = "1359-4184",
publisher = "Nature Publishing Group",
number = "8",

}

RIS

TY - JOUR

T1 - Addiction-related genes in gambling disorders

T2 - new insights from parallel human and pre-clinical models

AU - Lobo, D. S. S.

AU - Aleksandrova, L.

AU - Knight, Jo

AU - Casey, D. M.

AU - el-Guebaly, N.

AU - Nobrega, J. N.

AU - Kennedy, J. L.

PY - 2015/8

Y1 - 2015/8

N2 - Neurobiological research supports the characterization of disordered gambling (DG) as a behavioral addiction. Recently, an animal model of gambling behavior was developed (rat gambling task, rGT), expanding the available tools to investigate DG neurobiology. We investigated whether rGT performance and associated risk gene expression in the rat's brain could provide cross-translational understanding of the neuromolecular mechanisms of addiction in DG. We genotyped tagSNPs (single-nucleotide polymorphisms) in 38 addiction-related genes in 400 DG and 345 non-DG subjects. Genes with P<0.1 in the human association analyses were selected to be investigated in the animal arm to determine whether their mRNA expression in rats was associated with the rat's performance on the rGT. In humans, DG was significantly associated with tagSNPs in DRD3 (rs167771) and CAMK2D (rs3815072). Our results suggest that age and gender might moderate the association between CAMK2D and DG. Moderation effects could not be investigated due to sample power. In the animal arm, only the association between rGT performance and Drd3 expression remained significant after Bonferroni correction for 59 brain regions. As male rats were used, gender effects could not be investigated. Our results corroborate previous findings reporting the involvement of DRD3 receptor in addictions. To our knowledge, the use of human genetics, pre-clinical models and gene expression as a cross-translation paradigm has not previously been attempted in the field of addictions. The cross-validation of human findings in animal models is crucial for improving the translation of basic research into clinical treatments, which could accelerate neurobiological and pharmacological investigations in addictions.

AB - Neurobiological research supports the characterization of disordered gambling (DG) as a behavioral addiction. Recently, an animal model of gambling behavior was developed (rat gambling task, rGT), expanding the available tools to investigate DG neurobiology. We investigated whether rGT performance and associated risk gene expression in the rat's brain could provide cross-translational understanding of the neuromolecular mechanisms of addiction in DG. We genotyped tagSNPs (single-nucleotide polymorphisms) in 38 addiction-related genes in 400 DG and 345 non-DG subjects. Genes with P<0.1 in the human association analyses were selected to be investigated in the animal arm to determine whether their mRNA expression in rats was associated with the rat's performance on the rGT. In humans, DG was significantly associated with tagSNPs in DRD3 (rs167771) and CAMK2D (rs3815072). Our results suggest that age and gender might moderate the association between CAMK2D and DG. Moderation effects could not be investigated due to sample power. In the animal arm, only the association between rGT performance and Drd3 expression remained significant after Bonferroni correction for 59 brain regions. As male rats were used, gender effects could not be investigated. Our results corroborate previous findings reporting the involvement of DRD3 receptor in addictions. To our knowledge, the use of human genetics, pre-clinical models and gene expression as a cross-translation paradigm has not previously been attempted in the field of addictions. The cross-validation of human findings in animal models is crucial for improving the translation of basic research into clinical treatments, which could accelerate neurobiological and pharmacological investigations in addictions.

KW - Adult

KW - Animals

KW - Behavior, Addictive

KW - Brain

KW - Calcium-Calmodulin-Dependent Protein Kinase Type 2

KW - Disease Models, Animal

KW - Female

KW - Gambling

KW - Games, Experimental

KW - Genetic Association Studies

KW - Genetic Predisposition to Disease

KW - Humans

KW - Male

KW - Polymorphism, Single Nucleotide

KW - RNA, Messenger

KW - Rats, Sprague-Dawley

KW - Receptors, Dopamine D3

KW - Risk

U2 - 10.1038/mp.2014.113

DO - 10.1038/mp.2014.113

M3 - Journal article

C2 - 25266122

VL - 20

SP - 1002

EP - 1010

JO - Molecular Psychiatry

JF - Molecular Psychiatry

SN - 1359-4184

IS - 8

ER -