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
cocaine related behavior 1 (Cocrb1) spans 79.870166 - 121.405905 Mbp (NCBI Build 37) on Chr 1. Obtained from MGI (http://www.informatics.jax.org) by searching for QTLs containing the keyword .
QTL for METH responses for body temperature on Chr1 at D1Ncvs75 (79.87 Mbp , Build 37)
Description:
METH responses for body temperature spans 54.87 - 104.87 Mbp (NCBI Build 37) on Chr1. 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 chronic alcohol withdrawal severity on Chr1 at D1Mit46 (83.89 Mbp , Build 37)
Description:
chronic alcohol withdrawal severity spans 58.89 - 108.89 Mbp (NCBI Build 37) on Chr1. 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, Kyle Warren R, Crabbe JC, Metten P, Gene Erwin V, Belknap JK
QTL for METH responses for home cage activity on Chr1 at D1Ncvs41 (101.77 Mbp , Build 37)
Description:
METH responses for home cage activity spans 76.77 - 126.77 Mbp (NCBI Build 37) on Chr1. 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 activity-distance traveled 1. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (103894727)
QTL associated with autoimmune ovarian dysgenesis 3. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (109462445)
QTL associated with B.burgdorferi-associated arthritis 11. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (65896421)
Authors:
Roper RJ, Weis JJ, McCracken BA, Green CB, Ma Y, Weber KS, Fairbairn D, Butterfield RJ, Potter MR, Zachary JF, Doerge RW, Teuscher C
QTL associated with bone response to mechanical loading 8. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (78202934)
QTL associated with cyclophosphamide induced apoptosis. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (66992757)
Authors:
Bergman ML, Cilio CM, Penha-Gonalves C, Lamhamedi-Cherradi SE, Lfgren A, Colucci F, Lejon K, Garchon HJ, Holmberg D
QTL associated with cytokine deficiency colitis susceptibility 2. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (65899760)
QTL associated with chronic kidney disease blood pressure locus 1. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (112504774)
Authors:
Salzler HR, Griffiths R, Ruiz P, Chi L, Frey C, Marchuk DA, Rockman HA, Le TH
QTL associated with cocaine induced activation 5. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (88315827)
QTL associated with dependence on morphine QTL 1. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (90464815)
QTL associated with darker modification of yellow agouti QTL 2. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (73734337)
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