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
QTL Associated with Consumption level. On Chromosome 17 with a LOD score= 11.4, p-value =0.001. From a(n) intercross of QTL Associated with Consumption level. On Chromosome 20 with a LOD score= 8, p-value =0.001. From a(n) intercross of
Authors:
Marissal-Arvy N, Diane A, Moisan MP, Larue-Achagiotis C, Tridon C, Tome D, Fromentin G, Mormède P
QTL Associated with Consumption level. On Chromosome 12 with a LOD score= 2.1, p-value =0.68. From a(n) of QTL Associated with Alcohol response. On Chromosome 20 with a LOD score= 3.2, p-value =0.05. From a(n) intercoss of
Authors:
Radcliffe RA, Erwin VG, Bludeau P, Deng X, Fay T, Floyd KL, Deitrich RA
QTL Associated with blood insulin amount. On Chromosome 17 with a LOD score= 8.82, p-value =0.001. From a(n) intercross of QTL Associated with blood insulin amount. On Chromosome 20 with a LOD score= 6.38, p-value =0.001. From a(n) intercross of
Authors:
Marissal-Arvy N, Heliès JM, Tridon C, Moisan MP, Mormède P
Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that act as ligand-activated transcription factors. Although prescribed for dyslipidemia and type-II diabetes, PPAR agonists also possess anti-addictive characteristics. PPAR agonists decrease ethanol consumption and reduce withdrawal severity and susceptibility to stress-induced relapse in rodents. However, the cellular and molecular mechanisms facilitating these properties have yet to be investigated. We tested three PPAR agonists in a continuous access two-bottle choice (2BC) drinking paradigm and found that tesaglitazar (PPARα/γ; 1.5 mg/kg) and fenofibrate (PPARα; 150 mg/kg) decreased ethanol consumption in male C57BL/6J mice while bezafibrate (PPARα/γ/β; 75 mg/kg) did not. We hypothesized that changes in brain gene expression following fenofibrate and tesaglitazar treatment lead to reduced ethanol drinking. We studied unbiased genomic profiles in areas of the brain known to be important for ethanol dependence, the prefrontal cortex (PFC) and amygdala, and also profiled gene expression in liver. Genomic profiles from the non-effective bezafibrate treatment were used to filter out genes not associated with ethanol consumption. Because PPAR agonists are anti-inflammatory, they would be expected to target microglia and astrocytes. Surprisingly, PPAR agonists produced a strong neuronal signature in mouse brain, and fenofibrate and tesaglitazar (but not bezafibrate) targeted a subset of GABAergic interneurons in the amygdala. Weighted gene co-expression network analysis (WGCNA) revealed co-expression of treatment-significant genes. Functional annotation of these gene networks suggested that PPAR agonists might act via neuropeptide and dopaminergic signaling pathways in the amygdala. Our results reveal gene targets through which PPAR agonists can affect alcohol consumption behavior.
Authors:
Laura B Ferguson, Dana Most, Yuri A Blednov, R Adron Harris
GeneWeaver