Laboratory routine procedures such as handling, injection, gavage or transportation are stressful for animals and can influ- ence experimental results. Our investigations revealed that BALB/ c mice already show a measurable stress response to moderate laboratory stressors such as a single injection of physiological saline, which causes a transient lymphocytopenia and increased hypothalamus–pituitary–adrenal (HPA) axis activation. Changing the room within their home cage induced a comparable transient HPA axis activation and loss of circulating lymphocytes in these animals. More importantly, multiple injections, which are neces- sary in many drug intervention studies, led to increased basal glu- cocorticoid concentrations in the plasma, thereby veiling basal physiological parameters of ‘‘control” groups. Finally, we show that the shipment of commercially available BALB/c mice induces a long-lasting HPA axis activation and reduces gain in body weight during adolescence. Four weeks after shipment, mice already reveal an increased ACTH-induced corticosterone response but, controversially, no acute stress-induced glucocorticoid release. Using reserpine treatment, we identified catecholamines that sur- prisingly inhibit central HPA axis activation to prevent acute stress-induced corticosterone release in shipped animals. In sum- mary, repeated laboratory stressors and shipment of mice pro- foundly alter the characteristics of ‘‘control” groups and may also impede the interpretation of experimental data. Thus, exper- iments should be planned carefully to prevent side effects of laboratory routines on physiological parameters, which in the worst case could alter results. doi:10.1016/j.bbi.2009.06.037 33. Inhibition of IL-1 signaling blocks the anti-neurogenic and anhedonic actions of chronic stress R. Duman Yale University School of Medicine, 34 Park Street, New Haven, CT 06508, United States Previous studies demonstrate that IL-1 is increased in depressed patients, suggesting that elevated immune response and pro-inflam- matory cytokines contribute to the pathophysiology of mood disor- ders. The role of IL-1 in the cellular and behavioral effects of chronic unpredictable stress (CUS) was determined to test this hypothesis. We found that inhibition of IL-1/IL-1R1 blocks the decrease in hippo- campal neurogenesis and reverses the reduction in sucrose con- sumption resulting from CUS exposure. We also found that levels of anxiety were decreased in the IL-1R1 deletion mutants. Immuno- histochemical analysis demonstrated that IL-1R1 is expressed on neural progenitor cells and on mature granule cells in the dentate gyrus in vivo, and in adult neural progenitor cells in vitro. Incubation of adult neural progenitor cells in culture with IL-1 decreased the rate of cell proliferation, and this effect is mediated by NFkB signal- ing. Finally, we found that inhibition of NFkB signaling in rat blocks the anti-neurogenic and anhedonic effects of CUS. Taken together, the results provide strong support that IL-1/NFkB signaling, is an essential mediator of the negative effects of CUS on both neurogen- esis and sucrose consumption, and also contributes to basal levels of anxiety. These data also indicate that components of IL-1/NFkB sig- naling cascade are key targets for the treatment of stress, immune, and inflammatory related mood disorders. doi:10.1016/j.bbi.2009.06.038 34. Differential epigenetic effects of short and long term gluco- corticoid treatment on natural killer cell effector genes J.L. Eddy a , K.N. Krukowski a , T.L. Konley a , K. Loster a , L. Witek-Janusek b , H.L. Mathews a a Loyola University Chicago, Microbiology & Immunology, 2160 S. 1st Ave., Maywood, IL 60153, United States b Loyola University Chicago Niehoff School of Nursing, United States A diagnosis of breast cancer is accompanied by psychosocial dis- tress as well as glucocorticoid and immune dysregulation, character- ized by reduced natural killer cell activity (NKCA) and cytokine production. The purpose of this study was to evaluate glucocorticoid effects on the NK cell line, NK92. Cells were treated with a low con- centration of dexamethosone (dex) 10 À10 M for 96 h (extended exposure) or a high concentration 10 À6 M dex for 18 h (short expo- sure). Epigenetic patterns were assessed by chromatin immunopre- cipitation (ChIP) for histone acetylation (Ac), phosphorylation (P), and methylation (Me) measured by quantitative real time PCR. Both treatments reduced NKCA as judged by K562 lysis. Treatment for 96 h decreased histone(H)4 lysine(K)8Ac at the perforin promoter, 500 bp from the transcriptional start site (TSS). Reduced H4K8Ac was also seen 100 bp from the TSS in both the IFN-gamma and TNF-alpha promoter regions. H3S10 phosphorylation decreased in both the perforin and IFN-gamma promoter regions with a concom- itant decrease in H3K9 dimethylation. In contrast, short dex treat- ment increased H4K8Ac at both the perforin and IFN-gamma promoter regions. No effect of dex treatment was observed for H4K12. These data demonstrate the quantitative and differential effect of glucocorticoid treatment on immune effector genes. In vitro, extended dex exposure may mimic the effect of chronic stress on im- mune function and demonstrates a direct relationship between epi- genetic patterning and the immune dysregulation that accompanies psychosocial-distress. doi:10.1016/j.bbi.2009.06.039 35. Matrix metalloproteinase (MMP) response to exercise and training in hypertension K.M. Edwards, B. Sheu, B.G. Woods, S. Hong, A.H. Penn, G.W. Schmid-Schonbein, P.J. Mills Department of Psychiatry and Behavioral Medicine, University of California, San Diego, La Jolla, United States MMPs play a key role in vascular remodelling, breaking down the extracellular matrix (ECM). Elevated blood pressure (BP) is associ- ated with increased MMP levels and stiffening of the vessel walls caused by increased ECM deposits. These increases may have wide ramifications; we recently showed that MMPs also cleave cell sur- face molecules. Potentially, cleavage of insulin receptors by MMPs may reveal a pathway for insulin resistance development. We eval- uated effects of exercise training on levels of MMP-2, -8 and -9 in individuals with mildly elevated BP. Twenty-two sedentary subjects were randomly assigned to either an exercise only or exercise & diet 12-week intervention. Interventions reduced resting BP in both treatment groups (SBP/DBP: pre = 144/85, post = 132/76). MMP lev- els in plasma were determined at baseline and following 20-min treadmill exercise (65–70% VO2peak) prior to and following the interventions. MMP-8 and -9 levels increased significantly post- acute exercise (p’s < .005, g2’s > .43). MMP-8 also showed a signifi- cant intervention by acute exercise interaction (p = .05, g2 = .205) such that the change from baseline to post-exercise was reduced after 12-weeks exercise or exercise & diet intervention (pre-inter- S34 Abstracts / Brain, Behavior, and Immunity 23 (2009) S25–S64