H3 dopaminylation at glutamine 5 (H3Q5dop) plays a critical role in heroin-mediated transcriptional plasticity in midbrain regions, particularly the VTA. In rats undergoing abstinence from heroin self-administration (SA), we found acute and persistent accumulation of H3Q5dop in VTA. Attenuation of H3Q5dop during abstinence induced persistent changes in gene expression programs associated with neuronal signaling and dopaminergic function in heroin abstinence and led to reduced heroin-seeking behavior. Interestingly, the observed changes in molecular pathways after heroin SA showed significant yet reversed overlap with the same genes altered in cocaine SA.
Authors:
Sasha L Fulton, Swarup Mitra, Ashley E Lepack, Jennifer A Martin, Andrew F Stewart, Jacob Converse, Mason Hochstetler, David M Dietz, Ian Maze
Male (n = 13) and female (n = 12) Sprague Dawley rats responded under a fentanyl-versus-food choice procedure during daily 2-hour sessions. A total of 8 rats (4 male, 4 female) were trained to respond under a saline-versus-food choice procedure. In addition to the daily choice sessions, rats were provided extended access to fentanyl or saline during 12-hour self-administration sessions. After 2 weeks of this self-administration regimen, the nucleus accumbens and ventral tegmental area of a subset of rats were subjected to RNA sequencing. Sequence reads were trimmed to remove possible adapter sequences and nucleotides with poor quality using Trimmomatic v.0.36. The trimmed reads were mapped to the Rattus norvegicus Rnor6.0 reference genome available on Ensembl using the STAR aligner v.2.5.2b. Unique gene hit counts were calculated by using featureCounts from the Subread package v.1.5.2. After extraction of gene hit counts, the gene hit counts table was used for downstream differential expression analysis. Using DESeq2, a comparison of gene expression between groups of samples was performed. The Wald test was used to generate p values and log2 fold changes. Genes with an adjusted p value < .05 and absolute log2 fold change >1 were designated as DEGs for each comparison. From supplementary data 2.
Authors:
E Andrew Townsend, R Kijoon Kim, Hannah L Robinson, Samuel A Marsh, Matthew L Banks, Peter J Hamilton
LSI derived gene associations with keyword query Reelin. The list contains the top 300 genes associated with Reelin from the >13000 mouse homolog gene collection
Neocortex Gene Expression Correlates for BEC measured in BXD RI Females & Males obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The BEC measures blood ethanol concentration in mg/dl 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
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
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 8 (Cocrb8) spans 26.931283 - 76.931283 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 .
Alcohol preference QTL 1 spans 26931283-76931283 (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). Phenotypically extreme HAP1/LAP1 animals (n=96) and HAP2/LAP2 animals (n=48) were screened for microsatellite markers in chromosomal regions previously reported to influence alcohol preference phenotypes. Linkage to alcohol preference, Alpq1, mapped to chromosome 9 near D9Mit4 (29 cM) in the HAP1/LAP1 set and near D9Mit90 (9 cM) in the HAP2/LAP2 set. The Alpq1 QTL interval is broad and may contain more than 1 underlying gene. Drd2 at 28 cM is a potential candidate for Alpq1.
Authors:
Bice PJ, Foroud T, Carr LG, Zhang L, Liu L, Grahame NJ, Lumeng L, Li TK, Belknap JK
QTL for cocaine related behavior on Chr9 at D9Mit4 (52.27 Mbp , Build 37)
Description:
cocaine related behavior spans 27.27 - 77.27 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).
ethanol consumption 3 spans 27.27 - 77.27 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 Emv-3 (68.73 Mbp , Build 37)
Description:
differences in cocaine responsiveness spans 43.73 - 93.73 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 d (68.73 Mbp , Build 37)
Description:
differences in cocaine responsiveness spans 43.73 - 93.73 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 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).
Authors:
Tolliver BK, Belknap JK, Woods WE, Carney JM
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