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.
This gene sets comprises 30 genes that showed decreased expression in the adult rats exposed to prenatal ethanol. Background: By comparing gene expression during gestational ethanol exposure to gene expression of neurotransmission genes in the olfactory bulb of adolescent rats, study suggests that ethanol exposure via maternal diet predicted the propensity to ingest ethanol during adolescence.
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
Neocortex Gene Expression Correlates for ACTI05_ETHA measured in BXD RI Males obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The ACTI05_ETHA measures Distance traveled (cm) during the first five minutes 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
Striatum Gene Expression Correlates for LD_PCT_DISTLIGHT measured in BXD RI Males obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The LD_PCT_DISTLIGHT measures Light-Dark Box Percentage of distance traveled in light compartment 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 LD_PCT_LIGHT_TIME measured in BXD RI Males obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The LD_PCT_LIGHT_TIME measures Light-Dark Box Percentage time in light 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 LD_DARK_TIME measured in BXD RI Females & Males obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The LD_DARK_TIME measures Light-Dark Box Total seconds spent in dark compartment 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 LD_DARK_TIME measured in BXD RI Males obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The LD_DARK_TIME measures Light-Dark Box Total seconds spent in dark compartment 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 LD_LIGHT_TIME measured in BXD RI Females & Males obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The LD_LIGHT_TIME measures Light- Dark Box Total seconds spent in light compartment 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 LD_LIGHT_TIME measured in BXD RI Males obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The LD_LIGHT_TIME measures Light- Dark Box Total seconds spent in light compartment 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
Renthal W, Kumar A, Xiao G, Wilkinson M, Covington HE 3rd, Maze I, Sikder D, Robison AJ, LaPlant Q, Dietz DM, Russo SJ, Vialou V, Chakravarty S, Kodadek TJ, Stack A, Kabbaj M, Nestler EJ
cocaine related behavior 3 (Cocrb3) spans 114.482445 - 164.482445 Mbp (NCBI Build 37) on Chr 2. Obtained from MGI (http://www.informatics.jax.org) by searching for QTLs containing the keyword .
QTL for cocaine related behavior on Chr2 at D2Byu3 (139.48 Mbp , Build 37)
Description:
cocaine related behavior spans 114.48 - 164.48 Mbp (NCBI Build 37) on Chr2. 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 induced locomotion on Chr2 at NA (141.12 Mbp , Build 37)
Description:
ethanol induced locomotion spans 116.12 - 166.12 Mbp (NCBI Build 37) on Chr2. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
Authors:
Hitzemann R, Demarest K, Koyner J, Cipp L, Patel N, Rasmussen E, McCaughran J Jr
QTL for high-dose ethanol actions on Chr2 at D2Mit21 (159.38 Mbp , Build 37)
Description:
high-dose ethanol actions spans 134.38 - 184.38 Mbp (NCBI Build 37) on Chr2. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
Authors:
Erwin VG, Markel PD, Johnson TE, Gehle VM, Jones BC
QTL for METH responses for climbing on Chr2 at D2Mc1 (162.34 Mbp , Build 37)
Description:
METH responses for climbing spans 137.34 - 187.34 Mbp (NCBI Build 37) on Chr2. 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 nicotine sensitivity on Chr2 at D2Mit311 (162.39 Mbp , Build 37)
Description:
nicotine sensitivity spans 137.39 - 187.39 Mbp (NCBI Build 37) on Chr2. 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 Chr2 at D2Mit148 (183.66 Mbp , Build 37)
Description:
alcohol consumption spans 158.66 - 208.66 Mbp (NCBI Build 37) on Chr2. 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 alcohol preference locus on Chr2 at D2Mit74 (187.16 Mbp , Build 37)
Description:
alcohol preference locus spans 162.16 - 212.16 Mbp (NCBI Build 37) on Chr2. 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 Chr2 at D2Mit74 (187.16 Mbp , Build 37)
Description:
alcohol consumption spans 162.16 - 212.16 Mbp (NCBI Build 37) on Chr2. 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
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