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
Striatum Gene Expression Correlates for ST_MAX_120 measured in BXD RI Females obtained using GeneNetwork Striatum M430V2 (Apr05) 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_120 measured in BXD RI Males obtained using GeneNetwork Striatum M430V2 (Apr05) 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
Striatum Gene Expression Correlates for ST_MAX_70 measured in BXD RI Males 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
Striatum Gene Expression Correlates for ST_MAX_80 measured in BXD RI Males obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The ST_MAX_80 measures Maximum startle response to 80 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
Neocortex Gene Expression Correlates for MDMA_ACT_MDA_1 measured in BXD RI Females & Males obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The MDMA_ACT_MDA_1 measures Locomotor response of 10 mg/kg MDMA injected on Day 2 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
Whole Brain Gene Expression Correlates for SPD_TIMEDOWEL30SEC measured in BXD RI Males obtained using INIA Brain mRNA M430 (Jun06) RMA. The SPD_TIMEDOWEL30SEC measures Dowel Test - Time 30 Sec under the domain Porsolt. 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
A list of genes whose transcript abundance in the PFC changed significantly 4 hours after an acute dose of ethanol (1.8 g/kg). This list was generated using Fisher's Combined Probability test to analyze saline vs ethanol S-scores across B6 and D2 inbred strains (n=3) and 27 BXD RI lines (n=1). Statistical significance was determined using 1,000 permutations of S-score data and selecting for probe-sets with q-values < 0.05. Aaron Wolen 5-26-10.
Authors:
Wolen AR, Phillips CA, Langston MA, Putman AH, Vorster PJ, Bruce NA, York TP, Williams RW, Miles MF
cocaine related behavior 15 (Cocrb15) spans 70.807693 - 120.807693 Mbp (NCBI Build 37) on Chr 15. Obtained from MGI (http://www.informatics.jax.org) by searching for QTLs containing the keyword .
QTL for cocaine related behavior on Chr15 at D15Mit3 (83.88 Mbp , Build 37)
Description:
cocaine related behavior spans 58.88 - 108.88 Mbp (NCBI Build 37) on Chr15. 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 consumption on Chr15 at D15Mit105 (87.33 Mbp , Build 37)
Description:
alcohol consumption spans 62.33 - 112.33 Mbp (NCBI Build 37) on Chr15. 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 cocaine induced activation on Chr15 at NA (92.79 Mbp , Build 37)
Description:
cocaine induced activation spans 67.79 - 117.79 Mbp (NCBI Build 37) on Chr15. 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 home cage activity on Chr15 at D15Mit1 (93.20 Mbp , Build 37)
Description:
METH responses for home cage activity spans 68.20 - 118.20 Mbp (NCBI Build 37) on Chr15. 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 cocaine related behavior on Chr15 at D15Ncvs29 (95.81 Mbp , Build 37)
Description:
cocaine related behavior spans 70.81 - 120.81 Mbp (NCBI Build 37) on Chr15. 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 home cage activity on Chr15 at Spt1 (102.87 Mbp , Build 37)
Description:
METH responses for home cage activity spans 77.87 - 127.87 Mbp (NCBI Build 37) on Chr15. 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 cocaine seizure on Chr15 at D15Mit48 (105.10 Mbp , Build 37)
Description:
cocaine seizure spans 80.10 - 130.10 Mbp (NCBI Build 37) on Chr15. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
Ethanol Preference from BXD lines span 58586243-108586243. This interval was obtained by using an arbitrary interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org). Marker Loci associated with 10% Ethanol Preferences Drinking at p<0.05 (Two Tailed) in the BXD RI set and the Correlation Coefficient, p and Estimated LOD. D15Mit33 (83586243 NCBI 37) p=0.05, LOD=0.08 overall LOD BXD & Select Line 2.4.
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