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
Positional candidate genes for HOTPLATE_MEANOF2 in BXD RI Females & Males on Chr11
Description:
Position candidates for HOTPLATE_MEANOF2 measured in BXD RI Females & Males. HOTPLATE_MEANOF2 measures Thermal Nociception Hot Plate Avg of 2Trials under the domain Pain. The QTL found was a Suggestive QTL and spans 80 Mb to 90 Mb.
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
Positional candidate genes for TAILCLIP_LAT_SEC in BXD RI Females on Chr11
Description:
Position candidates for TAILCLIP_LAT_SEC measured in BXD RI Females. TAILCLIP_LAT_SEC measures Mechanical Nociception - Tail Clip Test under the domain Pain. The QTL found was a Significant QTL and spans 78 Mb to 82 Mb.
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 ACTI05_SAL measured in BXD RI Females & Males obtained using INIA Brain mRNA M430 (Jun06) RMA. The ACTI05_SAL measures Distance traveled (cm) during the first five minutes 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 LM_PS_INTVL2 measured in BXD RI Males obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The LM_PS_INTVL2 measures Activity in 30 second interval post 2nd 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
Hippocampus Gene Expression Correlates for ZM_LATENCY measured in BXD RI Females & Males obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The ZM_LATENCY measures Zero Maze - Latency to enter an open quadrant 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 ACTI10_SAL measured in BXD RI Females & Males obtained using INIA Brain mRNA M430 (Jun06) RMA. The ACTI10_SAL measures Distance traveled (cm) during the second 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
Whole Brain Gene Expression Correlates for ACTI10_SAL measured in BXD RI Males obtained using INIA Brain mRNA M430 (Jun06) RMA. The ACTI10_SAL measures Distance traveled (cm) during the second 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
Striatum Gene Expression Correlates for ADRE_LEFT_WT measured in BXD RI Females obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The ADRE_LEFT_WT measures Left adrenal weight under the domain Adrenals. 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 ADRE_RIGHT_WT measured in BXD RI Females & Males obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The ADRE_RIGHT_WT measures Right adrenal weight under the domain Adrenals. 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 ADRE_RIGHT_WT measured in BXD RI Females obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The ADRE_RIGHT_WT measures Right adrenal weight under the domain Adrenals. 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 COCA_TEST_VEHICLE measured in BXD RI Males obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The COCA_TEST_VEHICLE measures Cocaine CPP - Time (s) in saline paired compartment a 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 ENTRIES_CLOSED measured in BXD RI Females obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The ENTRIES_CLOSED measures Number of entries into closed arms of plus maze under the domain Ethanol. The correlates were thresholded at a p-value of less than 0.001.
Hippocampus Gene Expression Correlates for LM_PAIR1 measured in BXD RI Males obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The LM_PAIR1 measures Activity during 1st 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
Cerebellum Gene Expression Correlates for MDMA_ACT_SAL_1 measured in BXD RI Males obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The MDMA_ACT_SAL_1 measures Locomotor activity of mice on Day 1 under the domain MDMA. 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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