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
Genes identified as expressed higher (up) in the AJ strain than in the NOD strain. Differentially expressed genes had a Q-value < 0.05 following the Benjamini-Hochberg methodology for false discovery rates in the limma+voom pipeline within edgeR. Q-value is reported from the topTable function.
Genes identified as expressed higher (up) in the AJ strain than in the S129 strain. Differentially expressed genes had a Q-value < 0.05 following the Benjamini-Hochberg methodology for false discovery rates in the limma+voom pipeline within edgeR. Q-value is reported from the topTable function.
Genes identified as expressed higher (up) in the AJ strain than in the NOD strain. Differentially expressed genes had a Q-value < 0.05 following the Benjamini-Hochberg methodology for false discovery rates in the limma+voom pipeline within edgeR. Q-value is reported from the topTable function.
Genes identified as expressed higher (up) in the AJ strain than in the S129 strain. Differentially expressed genes had a Q-value < 0.05 following the Benjamini-Hochberg methodology for false discovery rates in the limma+voom pipeline within edgeR. Q-value is reported from the topTable function.
Genes identified as expressed lower (down) in the AJ strain than in the WSB strain. Differentially expressed genes had a Q-value < 0.05 following the Benjamini-Hochberg methodology for false discovery rates in the limma+voom pipeline within edgeR. Q-value is reported from the topTable function.
Genes identified as expressed lower (down) in the AJ strain than in the WSB strain. Differentially expressed genes had a Q-value < 0.05 following the Benjamini-Hochberg methodology for false discovery rates in the limma+voom pipeline within edgeR. Q-value is reported from the topTable function.
Genes identified as expressed lower (down) in the AJ strain than in the CAST strain. Differentially expressed genes had a Q-value < 0.05 following the Benjamini-Hochberg methodology for false discovery rates in the limma+voom pipeline within edgeR. Q-value is reported from the topTable function.
Genes identified as expressed lower (down) in the AJ strain than in the WSB strain. Differentially expressed genes had a Q-value < 0.05 following the Benjamini-Hochberg methodology for false discovery rates in the limma+voom pipeline within edgeR. Q-value is reported from the topTable function.
Genes identified as expressed lower (down) in the AJ strain than in the CAST strain. Differentially expressed genes had a Q-value < 0.05 following the Benjamini-Hochberg methodology for false discovery rates in the limma+voom pipeline within edgeR. Q-value is reported from the topTable function.
Genes identified as expressed higher (up) in the AJ strain than in the CAST strain. Differentially expressed genes had a Q-value < 0.05 following the Benjamini-Hochberg methodology for false discovery rates in the limma+voom pipeline within edgeR. Q-value is reported from the topTable function.
Genes identified as expressed higher (up) in the AJ strain than in the NZO strain. Differentially expressed genes had a Q-value < 0.05 following the Benjamini-Hochberg methodology for false discovery rates in the limma+voom pipeline within edgeR. Q-value is reported from the topTable function.
Genes identified as expressed lower (down) in the AJ strain than in the WSB strain. Differentially expressed genes had a Q-value < 0.05 following the Benjamini-Hochberg methodology for false discovery rates in the limma+voom pipeline within edgeR. Q-value is reported from the topTable function.
Genes identified as expressed higher (up) in the AJ strain than in the CAST strain. Differentially expressed genes had a Q-value < 0.05 following the Benjamini-Hochberg methodology for false discovery rates in the limma+voom pipeline within edgeR. Q-value is reported from the topTable function.
Genes identified as expressed higher (up) in the AJ strain than in the NZO strain. Differentially expressed genes had a Q-value < 0.05 following the Benjamini-Hochberg methodology for false discovery rates in the limma+voom pipeline within edgeR. Q-value is reported from the topTable function.
Microglia depletion and alcohol gene expression logFC
Description:
Alcohol abuse induces changes in microglia morphology and immune function, but whether microglia initiate or simply amplify the harmful effects of alcohol exposure is still a matter of debate. Here, we determine microglia function in acute and voluntary drinking behaviors using a colony-stimulating factor 1 receptor inhibitor (PLX5622). We show that microglia depletion does not alter the sedative or hypnotic effects of acute intoxication. Microglia depletion also does not change the escalation or maintenance of chronic voluntary alcohol consumption. Transcriptomic analysis revealed that although many immune genes have been implicated in alcohol abuse, down regulation of microglia genes does not necessitate changes in alcohol intake. Instead, microglia depletion and chronic alcohol result in compensatory upregulation of alcohol-responsive, reactive astrocyte genes, indicating astrocytes may play a role in regulation of these alcohol behaviors. Taken together, our behavioral and transcriptional data indicate that microglia are not theprimary effector cell responsible for regulation of acute and voluntary alcohol behaviors. Because microglia depletion did not regulate acute or voluntary alcohol behaviors, we hypothesized that these doses were insufficient to activate microglia and recruit them to an effector phenotype. Therefore, we used a model of repeated immune activation using polyinosinic:polycytidylic acid
We investigated the role of microglia in a mouse model of alcohol dependence using a colony stimulating factor 1 receptor inhibitor (PLX5622) to deplete microglia and a chronic intermittent ethanol vapor two-bottle choice drinking procedure. Additionally, we examined anxiety-like behavior during withdrawal. We then analyzed synaptic neuroadaptations in the central nucleus of the amygdala (CeA) and gene expression changes in the medial prefrontal cortex (mPFC) and CeA from the same animals used for behavioral studies.
Alcohol Microglia depletion in the medial prefrontal cortex q-value
Description:
dependence using a colony stimulating factor 1 receptor inhibitor (PLX5622) to deplete microglia and a chronic intermittent ethanol vapor two-bottle choice drinking procedure. Additionally, we examined anxiety-like behavior during withdrawal. We then analyzed synaptic neuroadaptations in the central nucleus of the amygdala (CeA) and gene expression changes in the medial prefrontal cortex (mPFC) and CeA from the same animals used for behavioral studies.
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.
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
Warning: You are not signed in. Adding these genesets to a project will create a guest account for you.
Guest accounts are temporary, and will be removed within 24 hours of creation. Guest accounts can be registered as full accounts, but you cannot associate a guest account with an existing account.
If you already have an account, you should sign into that account before proceeding.