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
Neocortex Gene Expression Correlates for ACTI10_ETHA measured in BXD RI Females obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The ACTI10_ETHA measures Distance traveled (cm) during the second five minute bin after 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
Whole Brain Gene Expression Correlates for LM_PS_INTVL3 measured in BXD RI Females obtained using INIA Brain mRNA M430 (Jun06) RMA. The LM_PS_INTVL3 measures Activity in 30 second interval post 3rd tone shock pairing 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 NEPCOUNT30 measured in BXD RI Females obtained using INIA Brain mRNA M430 (Jun06) RMA. The NEPCOUNT30 measures Novel environment locomotion (activity beam breaks) 15-30 min in the periphery 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
Whole Brain Gene Expression Correlates for NEPCOUNT30 measured in BXD RI Females obtained using INIA Brain mRNA M430 (Jun06) RMA. The NEPCOUNT30 measures Novel environment locomotion (activity beam breaks) 15-30 min in the periphery under the domain Morphine. The correlates were thresholded at a p-value of less than 0.001.
Whole Brain Gene Expression Correlates for NEPCOUNT30 measured in BXD RI Females obtained using INIA Brain mRNA M430 (Jun06) RMA. The NEPCOUNT30 measures Novel environment locomotion (activity beam breaks) 15-30 min in the periphery under the domain Cocaine. The correlates were thresholded at a p-value of less than 0.001.
Whole Brain Gene Expression Correlates for NEPDIST30 measured in BXD RI Females obtained using INIA Brain mRNA M430 (Jun06) RMA. The NEPDIST30 measures Novel environment distance (cm) travelled min 15-30 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
Whole Brain Gene Expression Correlates for NEPDIST30 measured in BXD RI Females obtained using INIA Brain mRNA M430 (Jun06) RMA. The NEPDIST30 measures Novel environment distance (cm) travelled min 15-30 under the domain Morphine. The correlates were thresholded at a p-value of less than 0.001.
Whole Brain Gene Expression Correlates for NEPDIST30 measured in BXD RI Females obtained using INIA Brain mRNA M430 (Jun06) RMA. The NEPDIST30 measures Novel environment distance (cm) travelled min 15-30 under the domain Cocaine. The correlates were thresholded at a p-value of less than 0.001.
Whole Brain Gene Expression Correlates for LM_CONTEXT_ACTIVITY measured in BXD RI Females & Males obtained using INIA Brain mRNA M430 (Jun06) RMA. 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
Hippocampus Gene Expression Correlates for OF_REAR_15_20 measured in BXD RI Males obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The OF_REAR_15_20 measures Open Field - Total rears 15-20 minutes 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 OF_REARS measured in BXD RI Males obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The OF_REARS measures Open Field - Total number of Rears 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 VOCA_THRESHOLD measured in BXD RI Females obtained using INIA Brain mRNA M430 (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
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 alcohol consumption on Chr1 at D1Mit167 (21.28 Mbp , Build 37)
Description:
alcohol consumption spans 0.00 - 46.28 Mbp (NCBI Build 37) on Chr1. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
Authors:
Vadasz C, Saito M, Gyetvai B, Mikics E, Vadasz C 2nd
QTL for alcohol preference locus on Chr1 at D1Mit295 (22.09 Mbp , Build 37)
Description:
alcohol preference locus spans 0.00 - 47.09 Mbp (NCBI Build 37) on Chr1. 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 Chr1 at D1Mit165 (22.12 Mbp , Build 37)
Description:
alcohol preference locus spans 0.00 - 47.12 Mbp (NCBI Build 37) on Chr1. 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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