title: Functional role of the N-terminal domain of ΔFosB in response to stress and drugs of abuse.
abstract: Previous work has implicated the transcription factor, ΔFosB, acting in the nucleus accumbens, in mediating the pro-rewarding effects of drugs of abuse such as cocaine as well as in mediating resilience to chronic social stress. However, the transgenic and viral gene transfer models used to establish these ΔFosB phenotypes express, in addition to ΔFosB, an alternative translation product of ΔFosB mRNA, termed Δ2ΔFosB, which lacks the N-terminal 78 aa present in ΔFosB. To study the possible contribution of Δ2ΔFosB to these drug and stress phenotypes, we prepared a viral vector that overexpresses a point mutant form of ΔFosB mRNA which cannot undergo alternative translation as well as a vector that overexpresses Δ2ΔFosB alone. Our results show that the mutant form of ΔFosB, when overexpressed in the nucleus accumbens, reproduces the enhancement of reward and of resilience seen with our earlier models, with no effects seen for Δ2ΔFosB. Overexpression of full length FosB, the other major product of the FosB gene, also has no effect. These findings confirm the unique role of ΔFosB in the nucleus accumbens in controlling responses to drugs of abuse and stress.
authors.affiliation: Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Department of Pharmacology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Y N
authors.initials: YN
authors.lastname: Ohnishi
authors.affiliation: Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Department of Pharmacology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Y H
authors.initials: YH
authors.lastname: Ohnishi
authors.affiliation: Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
authors.forename: V
authors.initials: V
authors.lastname: Vialou
authors.affiliation: Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
authors.forename: E
authors.initials: E
authors.lastname: Mouzon
authors.affiliation: Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
authors.forename: Q
authors.initials: Q
authors.lastname: LaPlant
authors.affiliation: Department of Pharmacology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Nishi
authors.affiliation: Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States. Electronic address: eric.nestler@mssm.edu.
authors.forename: E J
authors.initials: EJ
authors.lastname: Nestler
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004318:Doxycycline / Q000494:pharmacology; D005106:Exploratory Behavior / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics*; D009447:Neuroblastoma / Q000473:pathology; D009714:Nucleus Accumbens / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000737:chemistry / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D013315:Stress, Psychological / Q000235:genetics / Q000378:metabolism*; D019966:Substance-Related Disorders / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: C483819:Fosb protein, mouse; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D004318:Doxycycline
keywords: FosB; cocaine; social defeat stress; viral-mediated gene transfer; Δ2ΔFosB; ΔFosB