title: Reward devaluation and heroin escalation is associated with differential expression of CRF signaling genes.
abstract: One of the most damaging aspects of drug addiction is the degree to which natural rewards (family, friends, employment) are devalued in favor of seeking, obtaining and taking drugs. We have utilized an animal model of reward devaluation and heroin self-administration to explore the role of the coricotropin releasing factor (CRF) pathway. Given access to a saccharin cue followed by the opportunity to self-administer heroin, animals will parse into distinct phenotypes that suppress their saccharin intake (in favor of escalating heroin self-administration) or vice versa. We find that large saccharin suppressors (large heroin takers) demonstrate increased mRNA expression for elements of the CRF signaling pathway (CRF, CRF receptors and CRF binding protein) within the hippocampus, medial prefrontal cortex and the ventral tegmental area. Moreover, there were no gene expression changes of these components in the nucleus accumbens. Use of bisulfite conversion sequencing suggests that changes in CRF binding protein and CRF receptor gene expression may be mediated by differential promoter methylation.
authors.affiliation: Departments of Pharmacology, Penn State College of Medicine, Hershey, PA, United States.
authors.forename: Ashley J
authors.initials: AJ
authors.lastname: McFalls
authors.affiliation: Neural and Behavioral Sciences, Penn State College of Medicine, Hershey, PA, United States.
authors.forename: Caesar G
authors.initials: CG
authors.lastname: Imperio
authors.affiliation: Departments of Pharmacology, Penn State College of Medicine, Hershey, PA, United States.
authors.forename: Georgina
authors.initials: G
authors.lastname: Bixler
authors.affiliation: Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States.
authors.forename: Willard M
authors.initials: WM
authors.lastname: Freeman
authors.affiliation: Neural and Behavioral Sciences, Penn State College of Medicine, Hershey, PA, United States.
authors.forename: Patricia Sue
authors.initials: PS
authors.lastname: Grigson
authors.affiliation: Departments of Pharmacology, Penn State College of Medicine, Hershey, PA, United States. Electronic address: kvrana@hmc.psu.edu.
authors.forename: Kent E
authors.initials: KE
authors.lastname: Vrana
mesh_terms: D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000187:drug effects* / Q000378:metabolism* / Q000494:pharmacology; D003463:Cues; D003932:Heroin / Q000378:metabolism / Q000494:pharmacology; D006556:Heroin Dependence / Q000523:psychology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects; D051381:Rats; D012201:Reward; D012439:Saccharin / Q000008:administration & dosage; D012646:Self Administration; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000378:metabolism
chemical_list: D003932:Heroin; D003346:Corticotropin-Releasing Hormone; D012439:Saccharin
keywords: Addiction; DNA methylation; Gene-expression; Heroin; Reward devaluation