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Microarrays were used to investigate the gene expression profiles of different brain regions within the limbic system of mice which were selectively bred for either high (HAB) or low (LAB) anxiety-related behavior, and also show signs of comorbid depression-like behavior. This gene set contains significantly differentially expressed genes between HAB and LAB mice. Brain regions include the hypothalamic paraventricular nucleus (PVN), the supraoptic nucleus (SON), the basolateral (BLA) and central (CeA) amygdala, and the cingulate cortex (Cg), as well as the nucleus accumbens (NAc) and dentate gyrus (DG). Statistics reported as p-value.
Authors:
Czibere L, Baur LA, Wittmann A, Gemmeke K, Steiner A, Weber P, Ptz B, Ahmad N, Bunck M, Graf C, Widner R, Khne C, Panhuysen M, Hambsch B, Rieder G, Reinheckel T, Peters C, Holsboer F, Landgraf R, Deussing JM
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.
Affymetrix oligonucleotide arrays to assess gene expression in brains of mice selectively bred for differences in acute functional tolerance to an incoordinating effect of ethanol (HAFT mice, high acute functional tolerance; LAFT mice, low acute functional tolerance)
Sixty candidate genes upregulated in mouse midbrain 2 h post-ethanol treatment identified by microarray analysis were filtered by WebQTL analysis to derive the 49 genes shown
Genes reproducibly changed by Methamphetamine and/or Valproate treatment in mouse brain including PreFrontal Cortex, Amygdala, CaudatePutamen, Nucleus Accumbens and Ventral Tegmentum. (Tables 1-3 of paper)
Authors:
Ogden CA, Rich ME, Schork NJ, Paulus MP, Geyer MA, Lohr JB, Kuczenski R, Niculescu AB
Two strains of inbred mice, C57BL/6J and DBA/2J, were exposed to acute dose of ethanol and following microarray expression profiles in these two strains, study identified genes that are differentially expressed during ethanol treatment. This gene set comprises 30 ethanol-dependent genes that were upregulated in C57BL/6j mice during the study.
This gene set comprises 30 ethanol-dependent genes that were upregulated in DBA/2J mice during the study. Background: Two strains of inbred mice, C57BL/6J and DBA/2J, were exposed to acute dose of ethanol and following microarray expression profiles in these two strains, study identified genes that are differentially expressed during ethanol treatment.
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
Preference for 10% ethanol (g/kg) in tap water offered vs. tap water; means are the average of days 2 and 4 of a 4-day 24-hr access period by Phillips TJ , et al
QTL for METH responses for body temperature on Chr8 at D8Ncvs43 (95.66 Mbp , Build 37)
Description:
METH responses for body temperature spans 70.66 - 120.66 Mbp (NCBI Build 37) on Chr8. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
Chronic cocaine - Cocaine-paired (conditioned place preference) vs. Control (saline or cocaine-non-paired) DNA microarray All genes on microarray presented After the pre-conditioning phase where animals were allowed access to either compartment for 15 minutes for 4 consecutive days, the conditioning phase for the cocaine-paired groups and cocaine non-paired groups began, consisting of eight subsequent daily sessions. For both groups, cocaine (10 mg / kg) or saline injections were administered on alternate days. For the cocaine-paired groups, rats were immediately placed in one of the two compartments for 30 min with the door in place restricting a z transformation followed by z test and anova followed by Student-Newman-Keuls' post hoc test. Gene expression profile was assessed 24 h after the last conditioning session that corresponded to 48 h after last cocaine exposure, when drug has been eliminated from the body and transient transcriptional changes are likely to be minimal. Therefore, changes in gene expression at this time-point are likely to reflect longer lasting adaptations that may account for maintenance of cocaine-induced memories. The complete lists of normalized gene expression values for the hippocampus of saline-treated, cocaine non-paired and cocaine-paired groups are presented. Analyses revealed that 214 transcripts were differentially regulated in the hippocampus of cocaine-paired rats vs. non-paired and saline-treated controls. Cocaine-induced conditioned place preference caused significant increases in the expression of 151 genes and caused decreases in the expression of 63 genes. (NIF Table ID 130.1 [83])
Authors:
Krasnova IN, Li SM, Wood WH, McCoy MT, Prabhu VV, Becker KG, Katz JL, Cadet JL
Chronic cocaine - Cocaine-paired (conditioned place preference) vs. Control (saline or cocaine-non-paired) DNA microarray All genes on microarray presented After the pre-conditioning phase where animals were allowed access to either compartment for 15 minutes for 4 consecutive days, the conditioning phase for the cocaine-paired groups and cocaine non-paired groups began, consisting of eight subsequent daily sessions. For both groups, cocaine (10 mg / kg) or saline injections were administered on alternate days. For the cocaine-paired groups, rats were immediately placed in one of the two compartments for 30 min with the door in place restricting a z transformation followed by z test and anova followed by Student-Newman-Keuls' post hoc test. Gene expression profile was assessed 24 h after the last conditioning session that corresponded to 48 h after last cocaine exposure, when drug has been eliminated from the body and transient transcriptional changes are likely to be minimal. Therefore, changes in gene expression at this time-point are likely to reflect longer lasting adaptations that may account for maintenance of cocaine-induced memories. The complete lists of normalized gene expression values for the frontal cortex of saline-treated, cocaine non-paired and cocaine-paired groups are presented. Differences in the expression of 39 transcripts in the frontal cortex were related to the conditioned place preference paradigm. These include increases in the level of 22 genes and decreases in 17 genes. (NIF Table ID 130.3 [83.5])
Authors:
Krasnova IN, Li SM, Wood WH, McCoy MT, Prabhu VV, Becker KG, Katz JL, Cadet JL
Acute nicotine - Nicotine vs. Saline DNA microarray Change in gene expression All the animals received a subcutaneous saline injection once daily for 5 days to habituate them to the injection process. On day 6, animals received a subcutaneous injection of saline or nicotine in saline (2 mg / kg). Animals were killed by cervical dislocation 1, 2, 4, or 6 h following saline or nicotine injection. S-score (significance score) algorithm Change in expression at 6 hours. S-scores (significance score) > / = 2 or < / = -2 consistently in two adjacent time-points from the 1-, 2-, 4- and 6-h time-points. For a comparison between two arrays, an S-score of 2 or ?2 corresponds to a P value of 0.046. (NIF Table ID 339 [192])
Authors:
Chen X, Che Y, Zhang L, Putman AH, Damaj I, Martin BR, Kendler KS, Miles MF
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