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 HARGREAVES_MEANBOTH in BXD RI Females & Males on Chr4
Description:
Position candidates for HARGREAVES_MEANBOTH measured in BXD RI Females & Males. HARGREAVES_MEANBOTH measures Thermal Nociception Hargreaves' Test under the domain Pain. The QTL found was a Suggestive QTL and spans 44 Mb to 64 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 HARGREAVES_MEANBOTH in BXD RI Males on Chr4
Description:
Position candidates for HARGREAVES_MEANBOTH measured in BXD RI Males. HARGREAVES_MEANBOTH measures Thermal Nociception Hargreaves' Test under the domain Pain. The QTL found was a Suggestive QTL and spans 55 Mb to 60 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
Neocortex Gene Expression Correlates for ROTATRAIN_TIME measured in BXD RI Females & Males obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The ROTATRAIN_TIME measures Mean time on rotarod during training. 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
QTL for METH responses for climbing on Chr4 at Mltr3 (34.50 Mbp , Build 37)
Description:
METH responses for climbing spans 9.50 - 59.50 Mbp (NCBI Build 37) on Chr4. 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 METH responses for body temperature on Chr4 at D4Nds8 (40.90 Mbp , Build 37)
Description:
METH responses for body temperature spans 15.90 - 65.90 Mbp (NCBI Build 37) on Chr4. 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 METH responses for chewing on Chr4 at Lyb4 (46.47 Mbp , Build 37)
Description:
METH responses for chewing spans 21.47 - 71.47 Mbp (NCBI Build 37) on Chr4. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
Genes associated with Homo sapiens that interact with the MeSH term 'Vitamin K 3' (D024483). Incorporates data from 82 publications curated by the Comparative Toxicogenomics Database (CTD). ODE Gene scores represent number of supporting publications per gene.
Genes associated with Homo sapiens that interact with the MeSH term 'Copper Sulfate' (D019327). Incorporates data from 72 publications curated by the Comparative Toxicogenomics Database (CTD). ODE Gene scores represent number of supporting publications per gene.
Genes associated with Homo sapiens that interact with the MeSH term 'Tretinoin' (D014212). Incorporates data from 1 publications curated by the Comparative Toxicogenomics Database (CTD). ODE Gene scores represent number of supporting publications per gene.
Genes associated with Homo sapiens that interact with the MeSH term '7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide' (D015123). Incorporates data from 660 publications curated by the Comparative Toxicogenomics Database (CTD). ODE Gene scores represent number of supporting publications per gene.
Genes associated with Homo sapiens that interact with the MeSH term 'Cyclosporine' (D016572). Incorporates data from 1 publications curated by the Comparative Toxicogenomics Database (CTD). ODE Gene scores represent number of supporting publications per gene.
Genes associated with Homo sapiens that interact with the MeSH term 'arsenic trioxide' (C006632). Incorporates data from 3 publications curated by the Comparative Toxicogenomics Database (CTD). ODE Gene scores represent number of supporting publications per gene.
Genes associated with Platichthys flesus that interact with the MeSH term 'Cadmium Chloride' (D019256). Incorporates data from 4 publications curated by the Comparative Toxicogenomics Database (CTD). ODE Gene scores represent number of supporting publications per gene.
Genes associated with Homo sapiens that interact with the MeSH term 'Valproic Acid' (D014635). Incorporates data from 1238 publications curated by the Comparative Toxicogenomics Database (CTD). ODE Gene scores represent number of supporting publications per gene.
Genes associated with Homo sapiens that interact with the MeSH term 'Acetaminophen' (D000082). Incorporates data from 1 publications curated by the Comparative Toxicogenomics Database (CTD). ODE Gene scores represent number of supporting publications per gene.
Genes associated with Chloris chloris that interact with the MeSH term 'lipopolysaccharide, E coli O55-B5' (C482199). Incorporates data from 29 publications curated by the Comparative Toxicogenomics Database (CTD). ODE Gene scores represent number of supporting publications per gene.
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