The current study used two inbred mouse strains, C57BL/6 J and A/J, to investigate the genetics of behavioral responses to fentanyl. Mice were tested for conditioned place preference and fentanyl-induced locomotor activity. C57BL/6J mice formed a conditioned place preference to fentanyl injections and fentanyl increased their activity. Neither effect was noted in A/J mice. We conducted RNA-sequencing on the nucleus accumbens of mice used for fentanyl-induced locomotor activity. Surprisingly, we noted few differentially expressed genes using treatment as the main factor. However many genes differed between strains.
Authors:
Samuel J Harp, Mariangela Martini, Will Rosenow, Larry D Mesner, Hugh Johnson, Charles R Farber, Emilie F Rissman
BECs at LORR Recovery Chr# 9 rs13480854(7524005) with right flanking marker mCV23893269 (4062079) and left marker rs3663313 (123063108). This was mapped in 300 + (b6x129)F2 mice.
Ethanol Induced Ataxia Chr#9 rs3655717(65312971) with right flanking marker rs13480112(26413932) and left marker rs13480421(111761261). This was mapped in 300 + (b6x129)F2 mice.
Drug Naïve DO mice were tested for open field, light dark, hole board, novelty place preference before collecting the striatum. RNA-Seq data was analyzed with WGCNA using a soft thresholding power of 3 selected using the WGCNA scale-free topology R2 threshold of 0.9, signed network with a minimum module size of 30, correlation type is bicor, used numeric labels.
Drug Naïve DO mice were tested for open field, light dark, hole board, novelty place preference before collecting the striatum. RNA-Seq data was analyzed with paraclique using a bicor was used with a correlation coefficient threshold of |0.5| (unsigned), minimum seed clique size of 5, minimum finished paraclique size of 10, proportional glom factor of 0.2 for paraclique construction.
Gene expression changes in the post-mortem nucleus accumbens of chronic heroin abusers. Overall, little overlap in gene expression profiles was seen between the two drug-abusing cohorts: out of the approximately 39,000 transcripts investigated, the abundance of only 25 was significantly changed in both cocaine and heroin abusers, with nearly one-half of these being altered in opposite directions. 1050 Transcripts had different in abundance between the majority of heroin subjects and their matched controls.
Hippocampus Gene Expression Correlates for LM_PS_INTVL3 measured in BXD RI Females obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The LM_PS_INTVL3 measures Activity in 30 second interval post 3rd tone shock pairing 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
Hippocampus Gene Expression Correlates for ZM_ACTIVITY measured in BXD RI Females & Males obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The ZM_ACTIVITY measures Zero Maze - Total Activity count; number of beam breaks 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 ACTI10_SAL measured in BXD RI Females obtained using INIA Brain mRNA M430 (Jun06) RMA. The ACTI10_SAL measures Distance traveled (cm) during the second five minute bin after saline 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 ACTI20_SAL measured in BXD RI Females obtained using INIA Brain mRNA M430 (Jun06) RMA. The ACTI20_SAL measures Distance traveled (cm) during the fourth five minute bin after saline 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 AMCNT135 measured in BXD RI Females obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The AMCNT135 measures Morphine photocell counts minutes 120-135 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
Striatum Gene Expression Correlates for AMCNT165 measured in BXD RI Females obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The AMCNT165 measures Morphine photocell counts minutes 150-165 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
Hippocampus Gene Expression Correlates for ENTRIES_CLOSED measured in BXD RI Females obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The ENTRIES_CLOSED measures Number of entries into closed arms of plus maze under the domain Ethanol. The correlates were thresholded at a p-value of less than 0.001.
Striatum Gene Expression Correlates for VERCNT135 measured in BXD RI Females obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The VERCNT135 measures Morphine vertical activity counts minutes 120-135 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
Striatum Gene Expression Correlates for VERCNT165 measured in BXD RI Females obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The VERCNT165 measures Morphine vertical activity counts minutes 150-165 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
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).
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 METH responses for chewing on ChrX at DXNcvs10 (74.58 Mbp , Build 37)
Description:
METH responses for chewing spans 49.58 - 99.58 Mbp (NCBI Build 37) on ChrX. 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
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