title: Stress-induced activity in the locus coeruleus is not sensitive to stressor controllability.
abstract: An important factor in determining the adverse consequences of a stress experience is the degree to which an individual can exert control over the stressor. Stressor controllability is known to influence brain norepinephrine levels, but its impact on activity in noradrenergic cell bodies is unknown. In the present study we investigated whether noradrenergic neurons within the locus coeruleus (LC), the major source of forebrain norepinephrine, are sensitive to stressor controllability. We exposed adult male Sprague-Dawley rats to escapable or yoked inescapable tailshock and assessed LC activity by measuring changes in the immediate early gene c-fos and the enzyme tyrosine hydroxylase (TH). We used in situ hybridization to measure levels of c-fos mRNA, TH mRNA, and TH primary transcript in the LC. In all three cases stress exposure increased expression relative to an unstressed homecage control group, but expression did not differ between controllable and uncontrollable stress. To further examine whether stressor controllability influences the number of stress-responsive LC neurons we performed double-label immunohistochemistry for TH and Fos. Again we detected an overall effect of stress, which did not differ between controllable and uncontrollable stress. We conclude that exposure to stress robustly increases expression of TH and c-fos in the LC, but this effect is not influenced by stressor controllability. To the extent that the expression of these genes reflects degree of neuronal activation, our results suggest that stress-induced activity of noradrenergic cell bodies in the LC is not sensitive to stressor controllability.
authors.affiliation: Graduate Program in Neurobiology and Behavior, University of Washington, Seattle, Washington, USA.
authors.forename: Ross A
authors.initials: RA
authors.lastname: McDevitt
authors.forename: Patricia
authors.initials: P
authors.lastname: Szot
authors.forename: Michael V
authors.initials: MV
authors.lastname: Baratta
authors.forename: Sondra T
authors.initials: ST
authors.lastname: Bland
authors.forename: Sylvia S
authors.initials: SS
authors.lastname: White
authors.forename: Steven F
authors.initials: SF
authors.lastname: Maier
authors.forename: John F
authors.initials: JF
authors.lastname: Neumaier
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D004558:Electric Stimulation; D005239:Fear / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D006380:Helplessness, Learned; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008125:Locus Coeruleus / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000503:physiopathology*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology; D014836:Volition / Q000502:physiology*
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D014446:Tyrosine 3-Monooxygenase; D009638:Norepinephrine