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
Preference for 10% ethanol (g/kg) in tap water offered vs. tap water; means are the average of days 2 and 4 of a 4-day 24-hr access period by Phillips TJ , et al
Cerebellum Gene Expression Correlates for C1VCOUNT30 measured in BXD RI Females obtained using SJUT Cerebellum mRNA M430 (Mar05) 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
Cerebellum Gene Expression Correlates for C1VCOUNT60 measured in BXD RI Females obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The C1VCOUNT60 measures Open Field rears 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
Cerebellum Gene Expression Correlates for C2HDIS60 measured in BXD RI Females obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The C2HDIS60 measures Open Field Total34 horizontal distance (cm) 45-60 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
Cerebellum Gene Expression Correlates for C2VCOUNT30 measured in BXD RI Females obtained using SJUT Cerebellum mRNA M430 (Mar05) 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
Cerebellum Gene Expression Correlates for C2VCOUNT45 measured in BXD RI Females obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The C2VCOUNT45 measures Open Field rears 30-45 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
Cerebellum Gene Expression Correlates for C2VCOUNT60 measured in BXD RI Females obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The C2VCOUNT60 measures Open Field rears 45-60 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 DEFECATE measured in BXD RI Females & Males obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The DEFECATE measures Morphine Response - Defecation 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
Cerebellum Gene Expression Correlates for NEPVCOUNT30 measured in BXD RI Males obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The NEPVCOUNT30 measures Novel environment rears 15-30 min in the periphery 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
Cerebellum Gene Expression Correlates for NEPVCOUNT45 measured in BXD RI Males obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The NEPVCOUNT45 measures Novel environment rears 30-45 min in the periphery 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
Cerebellum Gene Expression Correlates for PNOVEL_VCOUNT_1 measured in BXD RI Males obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The PNOVEL_VCOUNT_1 measures Novel Open Field - TOTAL rears in the periphery 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
Cerebellum Gene Expression Correlates for ROTAETHA_DIFF measured in BXD RI Females & Males obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The ROTAETHA_DIFF measures Difference in time on rotarod between training and 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
Cerebellum Gene Expression Correlates for SALINE_VCOUNT_2 measured in BXD RI Females obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The SALINE_VCOUNT_2 measures Open Field TOTAL rears 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
Cerebellum Gene Expression Correlates for SALINE_VCOUNT_2 measured in BXD RI Males obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The SALINE_VCOUNT_2 measures Open Field TOTAL rears 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
Hippocampus Gene Expression Correlates for SEN_CHCL_ADIST_4 measured in BXD RI Males obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The SEN_CHCL_ADIST_4 measures Cocaine Sensitization - TOTAL locomotion ( cm in 1 hr) 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
Cerebellum Gene Expression Correlates for SEN_CHCL_VCOUNT_4 measured in BXD RI Females obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The SEN_CHCL_VCOUNT_4 measures Cocaine Sensitization - 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
Cerebellum Gene Expression Correlates for SEN_CHCL_VCOUNT_4 measured in BXD RI Males obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The SEN_CHCL_VCOUNT_4 measures Cocaine Sensitization - 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
Cerebellum Gene Expression Correlates for ST_MAX_120 measured in BXD RI Males obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The ST_MAX_120 measures Maximum startle to 120 db 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
Striatum Gene Expression Correlates for ST_MAX_70 measured in BXD RI Females obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The ST_MAX_70 measures Maximum startle response to 70 db 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
GeneWeaver