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 Males 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.
Hippocampus Gene Expression Correlates for CONSTRICT measured in BXD RI Females & Males obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The CONSTRICT measures Morphine Response Severity of abdominal constriction under the domain Morphine. 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 VONFREYTHRESHOLDMEAN measured in BXD RI Males 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
Striatum Gene Expression Correlates for COCA_TIME_BASELINE measured in BXD RI Females obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The COCA_TIME_BASELINE measures Cocaine CPP - Proportion of time spent in conditioned side prior to conditioning 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
Whole Brain Gene Expression Correlates for SPD_TIMEDOWEL30SEC measured in BXD RI Females & Males obtained using INIA Brain mRNA M430 (Jun06) RMA. The SPD_TIMEDOWEL30SEC measures Dowel Test - Time 30 Sec under the domain Porsolt. 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 VOCA_THRESHOLD measured in BXD RI Males obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) 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
Selection of known genes in IBD candidate loci, which show a two fold change at least in one comparison. CD or UC samples are referred to control specimens. The control expression values are given for the terminal ileum and the colon
Authors:
Zahn A, Moehle C, Langmann T, Ehehalt R, Autschbach F, Stremmel W, Schmitz G
Selection of known genes in IBD candidate loci, which show a two fold change at least in one comparison. CD or UC samples are referred to control specimens. The control expression values are given for the terminal ileum and the colon
Authors:
Zahn A, Moehle C, Langmann T, Ehehalt R, Autschbach F, Stremmel W, Schmitz G
Selection of known genes in IBD candidate loci, which show a two fold change at least in one comparison. CD or UC samples are referred to control specimens. The control expression values are given for the terminal ileum and the colon.
Authors:
Zahn A, Moehle C, Langmann T, Ehehalt R, Autschbach F, Stremmel W, Schmitz G
Selection of known genes in IBD candidate loci, which show a two fold change at least in one comparison. CD or UC samples are referred to control specimens. The control expression values are given for the terminal ileum and the colon.
Authors:
Zahn A, Moehle C, Langmann T, Ehehalt R, Autschbach F, Stremmel W, Schmitz G
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).
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