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
Whole Brain Gene Expression Correlates for ACTI15_ETHA measured in BXD RI Females obtained using INIA Brain mRNA M430 (Jun06) RMA. The ACTI15_ETHA measures Distance traveled (cm) during the third five minute bin after 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
Whole Brain Gene Expression Correlates for AMDIST180 measured in BXD RI Females obtained using INIA Brain mRNA M430 (Jun06) RMA. The AMDIST180 measures Morphine distance (cm) travelled minutes 165-180 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 OF_HAB_RATIO measured in BXD RI Males obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The OF_HAB_RATIO measures Open Field - Habituation ratio (First:Last intervals) 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 LM_ALT_CONTEXT measured in BXD RI Females & Males obtained using INIA Brain mRNA M430 (Jun06) 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
Whole Brain Gene Expression Correlates for LM_ALT_CONTEXT measured in BXD RI Males obtained using INIA Brain mRNA M430 (Jun06) 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
Whole Brain Gene Expression Correlates for NX_VCOUNT_3 measured in BXD RI Males obtained using INIA Brain mRNA M430 (Jun06) RMA. The NX_VCOUNT_3 measures Naloxone induced Morphine Withdrawal - TOTAL vertical activity 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
Whole Brain Gene Expression Correlates for SALIVA measured in BXD RI Females & Males obtained using INIA Brain mRNA M430 (Jun06) RMA. The SALIVA measures Morphine - Salivation 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 ZM_PCT_OPEN measured in BXD RI Males obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The ZM_PCT_OPEN measures Zero Maze - Percentage open time 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
QTL for METH responses for home cage activity on Chr10 at D10Mit144 (102.84 Mbp , Build 37)
Description:
METH responses for home cage activity spans 77.84 - 127.84 Mbp (NCBI Build 37) on Chr10. 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 Chr10 at Kcnc2 (114.10 Mbp , Build 37)
Description:
METH responses for body temperature spans 89.10 - 139.10 Mbp (NCBI Build 37) on Chr10. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
QTL associated with cystic fibrosis body weight 4. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (117587667)
QTL associated with cystic fibrosis modifier QTL 3. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (118098315)
QTL associated with estradiol regulated response QTL 4. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (117587667)
Authors:
Roper RJ, Griffith JS, Lyttle CR, Doerge RW, McNabb AW, Broadbent RE, Teuscher C
QTL associated with exploratory and excitability QTL 1. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (119449003)
Authors:
Zhang S, Lou Y, Amstein TM, Anyango M, Mohibullah N, Osoti A, Stancliffe D, King R, Iraqi F, Gershenfeld HK
QTL associated with femoral cross-sectional area 3. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (106528846)
Authors:
Klein RF, Turner RJ, Skinner LD, Vartanian KA, Serang M, Carlos AS, Shea M, Belknap JK, Orwoll ES
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