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.
Affymetrix oligonucleotide arrays to assess gene expression in brains of mice selectively bred for differences in acute functional tolerance to an incoordinating effect of ethanol (HAFT mice, high acute functional tolerance; LAFT mice, low acute functional tolerance)
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
QTL for METH responses for home cage activity on Chr5 at D5Ncvs56 (28.53 Mbp , Build 37)
Description:
METH responses for home cage activity spans 3.53 - 53.53 Mbp (NCBI Build 37) on Chr5. 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 alcohol preference locus on Chr5 at D5Mit11 (47.40 Mbp , Build 37)
Description:
alcohol preference locus spans 22.40 - 72.40 Mbp (NCBI Build 37) on Chr5. 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 alcohol preference locus on Chr5 at D5Mit11 (47.40 Mbp , Build 37)
Description:
alcohol preference locus spans 22.40 - 72.40 Mbp (NCBI Build 37) on Chr5. 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 climbing on Chr5 at D5Rik85 (47.40 Mbp , Build 37)
Description:
METH responses for climbing spans 22.40 - 72.40 Mbp (NCBI Build 37) on Chr5. 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 Acute ethanol sensitivity on Chr5 at NA (47.40 Mbp , Build 37)
Description:
Acute ethanol sensitivity spans 22.40 - 72.40 Mbp (NCBI Build 37) on Chr5. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
Authors:
Radcliffe RA, Bohl ML, Lowe MV, Cycowski CS, Wehner JM
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 Colinus virginianus that interact with the MeSH term '2,6-dinitrotoluene' (C023514). 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 'Selenomethionine' (D012645). 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 'Tretinoin' (D014212). 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 Oryzias latipes that interact with the MeSH term 'Estradiol' (D004958). 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 '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 'Aflatoxin B1' (D016604). Incorporates data from 5 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 'sodium arsenite' (C017947). Incorporates data from 15 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 '1-(4-(6-bromobenzo(1,3)dioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta(c)quinolin-8-yl)ethanone' (C517943). 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 'butyraldehyde' (C018475). Incorporates data from 7 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 'Parathion' (D010278). 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 'terbufos' (C012568). Incorporates data from 7 publications curated by the Comparative Toxicogenomics Database (CTD). ODE Gene scores represent number of supporting publications per gene.
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