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 & 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
Whole Brain Gene Expression Correlates for ACTI15_SAL measured in BXD RI Males obtained using INIA Brain mRNA M430 (Jun06) RMA. The ACTI15_SAL measures Distance traveled (cm) during the third five minute bin after saline 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 C1HCOUNT60 measured in BXD RI Males obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The C1HCOUNT60 measures Open Field locomotion 45-60 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
Hippocampus Gene Expression Correlates for C1VCOUNT15 measured in BXD RI Females obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The C1VCOUNT15 measures Open Field rears 0-15 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
Hippocampus Gene Expression Correlates for C1VCOUNT30 measured in BXD RI Females obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The C1VCOUNT30 measures Open Field rears 15-30 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
Hippocampus Gene Expression Correlates for C1VCOUNT30 measured in BXD RI Males obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The C1VCOUNT30 measures Open Field rears 15-30 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
Hippocampus Gene Expression Correlates for C1VCOUNT45 measured in BXD RI Males obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The C1VCOUNT45 measures Open Field rears 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
Hippocampus Gene Expression Correlates for C2VCOUNT30 measured in BXD RI Females obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The C2VCOUNT30 measures Open Field rears 15-30 min post 2nd 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
Hippocampus Gene Expression Correlates for LOC_CHCL_VCOUNT_3 measured in BXD RI Males obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The LOC_CHCL_VCOUNT_3 measures Cocaine Open Field TOTAL rears 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 NEPCOUNT60 measured in BXD RI Females obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The NEPCOUNT60 measures Novel environment locomotion (activity beam breaks) 45-60 min in the periphery under the domain Morphine. The correlates were thresholded at a p-value of less than 0.001.
Neocortex Gene Expression Correlates for NEPDIST60 measured in BXD RI Females obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The NEPDIST60 measures Novel environment locomotion (cm) 45-60 min in the periphery under the domain Morphine. The correlates were thresholded at a p-value of less than 0.001.
Neocortex Gene Expression Correlates for OF_CENTER_DIST_PCT measured in BXD RI Females obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The OF_CENTER_DIST_PCT measures Open Field - Percentage of total distance traveled in center 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
Neocortex Gene Expression Correlates for OF_CENTER_DIST_PCT measured in BXD RI Males obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The OF_CENTER_DIST_PCT measures Open Field - Percentage of total distance traveled in center 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
Neocortex Gene Expression Correlates for SHCOUNT45 measured in BXD RI Females obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The SHCOUNT45 measures Open Field - locomotion (activity beam breaks) 30-45 min post saline 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 SHCOUNT60 measured in BXD RI Females obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The SHCOUNT60 measures Open Field - locomotion (activity beam breaks) 45-60 min post saline 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 SHDIST45 measured in BXD RI Females obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The SHDIST45 measures Open Field - Total horizontal distance (cm) 30-45 min post saline (10 ml/kg) 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 SHDIST60 measured in BXD RI Females obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The SHDIST60 measures Open field locomotion - Saline- (cm) 45-60 min 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 ZM_ECLOSED measured in BXD RI Females & Males obtained using INIA Brain mRNA M430 (Jun06) RMA. The ZM_ECLOSED measures Zero Maze - total entries in closed quadrants 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
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