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
Striatum Gene Expression Correlates for LD_PCT_LIGHT_TIME measured in BXD RI Females obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The LD_PCT_LIGHT_TIME measures Light-Dark Box Percentage time in light under the domain Basal Behavior. 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
Striatum Gene Expression Correlates for LD_PCT_LIGHT_TIME measured in BXD RI Males obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The LD_PCT_LIGHT_TIME measures Light-Dark Box Percentage time in light under the domain Basal Behavior. 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
Whole Brain Gene Expression Correlates for OF_HAB_RATIO measured in BXD RI Males obtained using INIA Brain mRNA M430 (Jun06) RMA. The OF_HAB_RATIO measures Open Field - Habituation ratio (First:Last intervals) under the domain Basal Behavior. 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
Cerebellum Gene Expression Correlates for VOCA_THRESHOLD measured in BXD RI Males obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The VOCA_THRESHOLD measures Vocalization Threshold - shock intensity (mA) under the domain Stress Vocalization. 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
List of 40 discriminating genes between the UC-Ca and UC-NonCa groups.
Authors:
Watanabe T, Kobunai T, Toda E, Kanazawa T, Kazama Y, Tanaka J, Tanaka T, Yamamoto Y, Hata K, Kojima T, Yokoyama T, Konishi T, Okayama Y, Sugimoto Y, Oka T, Sasaki S, Ajioka Y, Muto T, Nagawa H
QTL for ethanol induced locomotion on Chr6 at NA (64.65 Mbp , Build 37)
Description:
ethanol induced locomotion spans 39.65 - 89.65 Mbp (NCBI Build 37) on Chr6. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
Authors:
Hitzemann R, Demarest K, Koyner J, Cipp L, Patel N, Rasmussen E, McCaughran J Jr
QTL for METH responses for home cage activity on Chr6 at D6Nds3 (67.84 Mbp , Build 37)
Description:
METH responses for home cage activity spans 42.84 - 92.84 Mbp (NCBI Build 37) on Chr6. 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 body temperature on Chr6 at D6MIt16 (67.84 Mbp , Build 37)
Description:
METH responses for body temperature spans 42.84 - 92.84 Mbp (NCBI Build 37) on Chr6. 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 body temperature on Chr6 at D6Nds2 (89.57 Mbp , Build 37)
Description:
METH responses for body temperature spans 64.57 - 114.57 Mbp (NCBI Build 37) on Chr6. 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 high-dose ethanol actions on Chr6 at D6Mit67 (91.93 Mbp , Build 37)
Description:
high-dose ethanol actions spans 66.93 - 116.93 Mbp (NCBI Build 37) on Chr6. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
Authors:
Erwin VG, Markel PD, Johnson TE, Gehle VM, Jones BC
QTL for differences in cocaine responsiveness on Chr6 at D6Nds2 (93.28 Mbp , Build 37)
Description:
differences in cocaine responsiveness spans 68.28 - 118.28 Mbp (NCBI Build 37) on Chr6. 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 high-dose ethanol actions on Chr6 at D6Mit36 (99.58 Mbp , Build 37)
Description:
high-dose ethanol actions spans 74.58 - 124.58 Mbp (NCBI Build 37) on Chr6. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
Authors:
Erwin VG, Markel PD, Johnson TE, Gehle VM, Jones BC
QTL for METH responses for home cage activity on Chr6 at II5ra (101.18 Mbp , Build 37)
Description:
METH responses for home cage activity spans 76.18 - 126.18 Mbp (NCBI Build 37) on Chr6. 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 'Fluorouracil' (D005472). Incorporates data from 99 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 'vorinostat' (C111237). Incorporates data from 13 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 'Cyclosporine' (D016572). 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 '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.
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