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
Striatum Gene Expression Correlates for VONFREYTHRESHOLDMEAN measured in BXD RI Females & Males obtained using GeneNetwork Striatum M430V2 (Apr05) 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 NEPDIST15 measured in BXD RI Males obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The NEPDIST15 measures Novel environment distance (cm) travelled minutes 0-15 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
Striatum Gene Expression Correlates for NEPDIST15 measured in BXD RI Males obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The NEPDIST15 measures Novel environment distance (cm) travelled minutes 0-15 under the domain Morphine. The correlates were thresholded at a p-value of less than 0.001.
Cerebellum Gene Expression Correlates for AMCNT105 measured in BXD RI Females & Males obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The AMCNT105 measures Morphine photocell counts minutes 90-105 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 AMCNT105 measured in BXD RI Males obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The AMCNT105 measures Morphine photocell counts minutes 90-105 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 AMCNT15 measured in BXD RI Females obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The AMCNT15 measures Morphine photocell counts minutes 0-15 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 AMCNT90 measured in BXD RI Males obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The AMCNT90 measures Morphine photocell counts minutes 75-90 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
Neocortex Gene Expression Correlates for OF_REAR_15_20 measured in BXD RI Females obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. 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
Neocortex Gene Expression Correlates for OF_REAR_5_10 measured in BXD RI Females obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The OF_REAR_5_10 measures Open Field - Total rears 5-10 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
Neocortex Gene Expression Correlates for OF_REARS measured in BXD RI Females obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. 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
Hippocampus Gene Expression Correlates for URINE measured in BXD RI Males obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The URINE measures Novel Open Field Number of urinations 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 VERCNT105 measured in BXD RI Males obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The VERCNT105 measures Morphine vertical activity counts minutes 90-105 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 VERCNT75 measured in BXD RI Males obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The VERCNT75 measures Morphine vertical activity counts minutes 60-75 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 VERCNT90 measured in BXD RI Males obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The VERCNT90 measures Morphine vertical activity counts minutes 75-90 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
Heterozygote mice from a hybrid cross of C57BL/6J and FVB/NJ had heightened EtOH consumption, preference or blood EtOH concentration compared to either homozygous groups. The magnitude of dominant deviation on Chr. 11, as noted in Fig. 9, was measured after a drinking in the dark paradigm, 24hr two-bottle-choice and subsequent blood ethanol concentration measurement.
Authors:
Phillips TJ, Reed C, Burkhart-Kasch S, Li N, Hitzemann R, Yu CH, Brown LL, Helms ML, Crabbe JC, Belknap JK
cocaine related behavior 12 (Cocrb12) spans 85.558736 - 135.558736 Mbp (NCBI Build 37) on Chr 11. Obtained from MGI (http://www.informatics.jax.org) by searching for QTLs containing the keyword .
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