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 ACTI_DIFF_05 measured in BXD RI Males obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The ACTI_DIFF_05 measures Difference in distance traveled (cm) during the first five min (saline-ethanol) under the domain Ethanol. 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
Hippocampus Gene Expression Correlates for C1HCOUNT45 measured in BXD RI Females obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The C1HCOUNT45 measures Open Field locomotion 30-45 min post cocaine under the domain Cocaine. 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
Neocortex Gene Expression Correlates for LD_LIGHT_DIST measured in BXD RI Males obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The LD_LIGHT_DIST measures Light-Dark Box Total distance traveled in light compartment 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
Hippocampus Gene Expression Correlates for NOVEL_RATIO measured in BXD RI Females obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The NOVEL_RATIO measures Novel Open Field - locomotion in the periphery as a function of total locomotion. under the domain Cocaine. 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
Hippocampus Gene Expression Correlates for NOVEL_RATIO measured in BXD RI Males obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The NOVEL_RATIO measures Novel Open Field - locomotion in the periphery as a function of total locomotion. under the domain Cocaine. 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
Neocortex Gene Expression Correlates for LM_CONTEXT_ACTIVITY measured in BXD RI Females & Males obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The LM_CONTEXT_ACTIVITY measures Contextual activity in fear conditioning apparatus 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
Renthal W, Kumar A, Xiao G, Wilkinson M, Covington HE 3rd, Maze I, Sikder D, Robison AJ, LaPlant Q, Dietz DM, Russo SJ, Vialou V, Chakravarty S, Kodadek TJ, Stack A, Kabbaj M, Nestler EJ
QTL for nicotine sensitivity on Chr7 at D7Mit66 (116.91 Mbp , Build 37)
Description:
nicotine sensitivity spans 91.91 - 141.91 Mbp (NCBI Build 37) on Chr7. 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 Chr7 at D7Mit105 (126.73 Mbp , Build 37)
Description:
alcohol preference locus spans 101.73 - 151.73 Mbp (NCBI Build 37) on Chr7. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
alcohol preference locus 14, female specific at D7Mit105 with a LOD score of 1.84 (p < 0.004) spans and preference correlation of 0.591 101.73 - 151.73 Mbp (NCBI Build 37) on Chr7. 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 Chr7 at D7Mit12 (129.57 Mbp , Build 37)
Description:
METH responses for home cage activity spans 104.57 - 154.57 Mbp (NCBI Build 37) on Chr7. 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 Chr7 at Xmv76 (137.02 Mbp , Build 37)
Description:
METH responses for body temperature spans 112.02 - 162.02 Mbp (NCBI Build 37) on Chr7. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
Acute nicotine - Nicotine vs. Saline DNA microarray Change in gene expression All the animals received a subcutaneous saline injection once daily for 5 days to habituate them to the injection process. On day 6, animals received a subcutaneous injection of saline or nicotine in saline (2 mg / kg). Animals were killed by cervical dislocation 1, 2, 4, or 6 h following saline or nicotine injection. S-score (significance score) algorithm Change in expression at 6 hours. S-scores (significance score) > / = 2 or < / = -2 consistently in two adjacent time-points from the 1-, 2-, 4- and 6-h time-points. For a comparison between two arrays, an S-score of 2 or ?2 corresponds to a P value of 0.046. (NIF Table ID 339 [192])
Authors:
Chen X, Che Y, Zhang L, Putman AH, Damaj I, Martin BR, Kendler KS, Miles MF
Genes associated with Homo sapiens that interact with the MeSH term 'Theophylline' (D013806). 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 Micropterus salmoides that interact with the MeSH term 'Dieldrin' (D004026). 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 'Plant Oils' (D010938). 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 'Copper Sulfate' (D019327). Incorporates data from 72 publications curated by the Comparative Toxicogenomics Database (CTD). ODE Gene scores represent number of supporting publications per gene.
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