Activation of the mesolimbic dopamine reward pathway by acute ethanol produces reinforcement and changes in gene expression that appear to be crucial to the molecular basis for adaptive behaviors and addiction. The inbred mouse strains DBA/2J and C57BL/6J exhibit contrasting acute behavioral responses to ethanol. We used oligonucleotide microarrays and bioinformatics methods to characterize patterns of gene expression in three brain regions of the mesolimbic reward pathway of these strains. Expression profiling included examination of both differences in gene expression 4 h after saline injection or acute ethanol (2 g/kg). Using a rigorous stepwise method for microarray analysis, we identified 788 genes differentially expressed in control DBA/2J versus C57BL/6J mice and 307 ethanol-regulated genes in the nucleus accumbens, prefrontal cortex, and ventral tegmental area. There were strikingly divergent patterns of ethanol-responsive gene expression in the two strains. Ethanol-responsive genes also showed clustering at discrete chromosomal regions, suggesting local chromatin effects in regulation. Ethanol-regulated genes were generally related to neuroplasticity, but regulation of discrete functional groups and pathways was brain region specific: glucocorticoid signaling, neurogenesis, and myelination in the prefrontal cortex; neuropeptide signaling and developmental genes, including factor Bdnf, in the nucleus accumbens; and retinoic acid signaling in the ventral tegmental area. Bioinformatics analysis identified several potential candidate genes for quantitative trait loci linked to ethanol behaviors, further supporting a role for expression profiling in identifying genes for complex traits. Brain region-specific changes in signaling and neuronal plasticity may be critical components in development of lasting ethanol behavioral phenotypes such as dependence, sensitization, and craving.
A list of the 307 genes found to be upregulated or downregulated by ethanol in PFC, VTA or NA of B6 or D2 mice. ID number represents cluster membership from Figure 4.
Authors:
Kerns RT, Ravindranathan A, Hassan S, Cage MP, York T, Sikela JM, Williams RW, Miles MF
Hippocampus Gene Expression Correlates for VONFREYTHRESHOLDMEAN measured in BXD RI Females obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The VONFREYTHRESHOLDMEAN measures Mechanical Sensitivity-Von Frey Threshold under the domain Pain. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
QTL for differences in cocaine responsiveness on Chr17 at Ck-2 (45.25 Mbp , Build 37)
Description:
differences in cocaine responsiveness spans 20.25 - 70.25 Mbp (NCBI Build 37) on Chr17. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
QTL for differences in cocaine responsiveness on Chr17 at D17MIt7 (51.99 Mbp , Build 37)
Description:
differences in cocaine responsiveness spans 26.99 - 76.99 Mbp (NCBI Build 37) on Chr17. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
QTL for t-psl on Chr17 at Hp (53.97 Mbp , Build 37)
Description:
t-psl spans 28.97 - 78.97 Mbp (NCBI Build 37) on Chr17. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
QTL for differences in cocaine responsiveness on Chr17 at DI7Mft3 (64.20 Mbp , Build 37)
Description:
differences in cocaine responsiveness spans 39.20 - 89.20 Mbp (NCBI Build 37) on Chr17. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
QTL for METH responses for home cage activity on Chr17 at D17Mit3 (70.84 Mbp , Build 37)
Description:
METH responses for home cage activity spans 45.84 - 95.84 Mbp (NCBI Build 37) on Chr17. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
QTL for METH responses for chewing on Chr17 at Hprt-ps1 (77.06 Mbp , Build 37)
Description:
METH responses for chewing spans 52.06 - 102.06 Mbp (NCBI Build 37) on Chr17. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
Genes associated with Homo sapiens that interact with the MeSH term '5-dihydrocortisone' (C045993). Incorporates data from 1538 publications curated by the Comparative Toxicogenomics Database (CTD). ODE Gene scores represent number of supporting publications per gene.
Genes associated with Homo sapiens that interact with the MeSH term '(6-(4-(2-piperidin-1-ylethoxy)phenyl))-3-pyridin-4-ylpyrazolo(1,5-a)pyrimidine' (C516138). Incorporates data from 3 publications curated by the Comparative Toxicogenomics Database (CTD). ODE Gene scores represent number of supporting publications per gene.
Genes associated with Homo sapiens that interact with the MeSH term 'Amiodarone' (D000638). Incorporates data from 38 publications curated by the Comparative Toxicogenomics Database (CTD). ODE Gene scores represent number of supporting publications per gene.
Genes associated with Homo sapiens that interact with the MeSH term 'Zinc Sulfate' (D019287). Incorporates data from 14 publications curated by the Comparative Toxicogenomics Database (CTD). ODE Gene scores represent number of supporting publications per gene.
Genes associated with Homo sapiens that interact with the MeSH term 'nickel sulfate' (C029938). Incorporates data from 1 publications curated by the Comparative Toxicogenomics Database (CTD). ODE Gene scores represent number of supporting publications per gene.
Genes associated with Homo sapiens that interact with the MeSH term 'alitretinoin' (C103303). Incorporates data from 8 publications curated by the Comparative Toxicogenomics Database (CTD). ODE Gene scores represent number of supporting publications per gene.
Genes associated with Homo sapiens that interact with the MeSH term 'pentanal' (C046012). Incorporates data from 2 publications curated by the Comparative Toxicogenomics Database (CTD). ODE Gene scores represent number of supporting publications per gene.
Genes associated with Homo sapiens that interact with the MeSH term 'propionaldehyde' (C005556). Incorporates data from 1 publications curated by the Comparative Toxicogenomics Database (CTD). ODE Gene scores represent number of supporting publications per gene.
Genes associated with Homo sapiens that interact with the MeSH term '3,4,5,3',4'-pentachlorobiphenyl' (C023035). Incorporates data from 644 publications curated by the Comparative Toxicogenomics Database (CTD). ODE Gene scores represent number of supporting publications per gene.
Genes associated with Homo sapiens that interact with the MeSH term '4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide' (C459179). Incorporates data from 9 publications curated by the Comparative Toxicogenomics Database (CTD). ODE Gene scores represent number of supporting publications per gene.
Genes associated with Homo sapiens that interact with the MeSH term 'Atrazine' (D001280). Incorporates data from 48 publications curated by the Comparative Toxicogenomics Database (CTD). ODE Gene scores represent number of supporting publications per gene.
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