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 NX_ACOUNT_3 measured in BXD RI Females & Males obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The NX_ACOUNT_3 measures Naloxone induced Morphine Withdrawal TOTAL photocell counts in 15 minutes 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
Hippocampus Gene Expression Correlates for OF_DIST_15_20 measured in BXD RI Females obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The OF_DIST_15_20 measures Open Field - Total distance traveled 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
Whole Brain Gene Expression Correlates for ADUL_RMS_BRDU measured in BXD RI Females obtained using INIA Brain mRNA M430 (Jun06) RMA. The ADUL_RMS_BRDU measures Neurogenesis- BrdU labeled new neurons in Adult Rostral Migratory Stream 1 hr post BrdU under the domain Neurogenesis. 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 HAND_4HOURS measured in BXD RI Females & Males obtained using INIA Brain mRNA M430 (Jun06) RMA. The HAND_4HOURS measures Handling induced convulsions 4 hrs after ethanol under the domain Ethanol HIC. 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 LM_ALT_CONTEXT measured in BXD RI Males obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The LM_ALT_CONTEXT measures Activity in altered context in fear conditioning apparatus 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 LM_BASELINE measured in BXD RI Females obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The LM_BASELINE measures Baseline activity in fear conditioning apparatus 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 LM_CONTEXT_ACTIVITY measured in BXD RI Females obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The LM_CONTEXT_ACTIVITY measures Contextual activity in fear conditioning apparatus 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
cocaine related behavior 10 (Cocrb10) spans 93.149752 - 143.149752 Mbp (NCBI Build 37) on Chr 9. Obtained from MGI (http://www.informatics.jax.org) by searching for QTLs containing the keyword .
cocaine related behavior 9 (Cocrb9) spans 49.746096 - 99.746096 Mbp (NCBI Build 37) on Chr 9. Obtained from MGI (http://www.informatics.jax.org) by searching for QTLs containing the keyword .
QTL for differences in cocaine responsiveness on Chr9 at Gsta (69.74 Mbp , Build 37)
Description:
differences in cocaine responsiveness spans 44.74 - 94.74 Mbp (NCBI Build 37) on Chr9. 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 Chr9 at D9Mit54 (69.74 Mbp , Build 37)
Description:
alcohol consumption spans 44.74 - 94.74 Mbp (NCBI Build 37) on Chr9. 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 differences in cocaine responsiveness on Chr9 at D9M!t8 (71.95 Mbp , Build 37)
Description:
differences in cocaine responsiveness spans 46.95 - 96.95 Mbp (NCBI Build 37) on Chr9. 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 differences in cocaine responsiveness on Chr9 at D9Nds2 (73.94 Mbp , Build 37)
Description:
differences in cocaine responsiveness spans 48.94 - 98.94 Mbp (NCBI Build 37) on Chr9. 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 behaviol on Chr9 at D9Ncvs47 (74.75 Mbp , Build 37)
Description:
cocaine related behaviol spans 49.75 - 99.75 Mbp (NCBI Build 37) on Chr9. 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 morphine antinociception on Chr9 at D9Mit8 (74.75 Mbp , Build 37)
Description:
morphine antinociception spans 49.75 - 99.75 Mbp (NCBI Build 37) on Chr9. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
Authors:
Bergeson SE, Helms ML, O\'Toole LA, Jarvis MW, Hain HS, Mogil JS, Belknap JK
QTL for differences in cocaine responsiveness on Chr9 at Pgm-3 (77.23 Mbp , Build 37)
Description:
differences in cocaine responsiveness spans 52.23 - 102.23 Mbp (NCBI Build 37) on Chr9. 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 differences in cocaine responsiveness on Chr9 at Mod-i (80.19 Mbp , Build 37)
Description:
differences in cocaine responsiveness spans 55.19 - 105.19 Mbp (NCBI Build 37) on Chr9. 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 differences in cocaine responsiveness on Chr9 at Crbp-2 (82.37 Mbp , Build 37)
Description:
differences in cocaine responsiveness spans 57.37 - 107.37 Mbp (NCBI Build 37) on Chr9. 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 ethanol withdrawal on Chr9 at D9Ncvs40 (85.16 Mbp , Build 37)
Description:
ethanol withdrawal spans 60.16 - 110.16 Mbp (NCBI Build 37) on Chr9. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
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