title: Induction of deltaFosB in the periaqueductal gray by stress promotes active coping responses.
abstract: We analyzed the influence of the transcription factor DeltaFosB on learned helplessness, an animal model of affective disorder wherein a subset of mice exposed to inescapable stress (IS) develop a deficit in escape behavior. Repeated IS induces DeltaFosB in the ventrolateral periaqueductal gray (vlPAG), and levels of the protein are highly predictive of an individual's subsequent behavorial deficit-with the strongest DeltaFosB induction observed in the most resilient animals. Induction of DeltaFosB by IS predominates in substance P-positive neurons in the vlPAG, and the substance P gene, a direct target for DeltaFosB, is downregulated upon DeltaFosB induction. Local overexpression of DeltaFosB in the vlPAG using viral-mediated gene transfer dramatically reduces depression-like behaviors and inhibits stress-induced release of substance P. These results indicate that IS-induced accumulation of DeltaFosB in the vlPAG desensitizes substance P neurons enriched in this area and opposes behavioral despair by promoting active defense responses.
authors.affiliation: Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9070, USA.
authors.forename: Olivier
authors.initials: O
authors.lastname: Berton
authors.forename: Herbert E
authors.initials: HE
authors.lastname: Covington
authors.forename: Karl
authors.initials: K
authors.lastname: Ebner
authors.forename: Nadia M
authors.initials: NM
authors.lastname: Tsankova
authors.forename: Tiffany L
authors.initials: TL
authors.lastname: Carle
authors.forename: Paula
authors.initials: P
authors.lastname: Ulery
authors.forename: Akshay
authors.initials: A
authors.lastname: Bhonsle
authors.forename: Michel
authors.initials: M
authors.lastname: Barrot
authors.forename: Vaishnav
authors.initials: V
authors.lastname: Krishnan
authors.forename: Georg M
authors.initials: GM
authors.lastname: Singewald
authors.forename: Nicolas
authors.initials: N
authors.lastname: Singewald
authors.forename: Shari
authors.initials: S
authors.lastname: Birnbaum
authors.forename: Rachael L
authors.initials: RL
authors.lastname: Neve
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Nestler
mesh_terms: D000222:Adaptation, Physiological; D000223:Adaptation, Psychological / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D004924:Escape Reaction / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D006380:Helplessness, Learned; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism; D009714:Nucleus Accumbens / Q000378:metabolism; D010487:Periaqueductal Gray / Q000166:cytology / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism
chemical_list: C483819:Fosb protein, mouse; C483820:Fosb protein, rat; D016760:Proto-Oncogene Proteins c-fos; D013373:Substance P