title: Mouse handling limits the impact of stress on metabolic endpoints.
abstract: Studies focused on end-points that are confounded by stress are best performed under minimally stressful conditions. The objective of this study was to demonstrate the impact of handling designed to reduce animal stress on measurements of glucose tolerance. A cohort of mice (CD1.C57BL/6) naïve to any specific handling was subjected to either a previously described "cup" handling method, or a "tail-picked" method in which the animals were picked up by the tail (as is common for metabolic studies). Following training, an elevated plus maze (EPM) test was performed followed by measurement of blood glucose and plasma corticosterone. A second cohort (CD1.C57BL/6) was rendered obese by exposure to a high fat diet, handled with either the tail-picked or cup method and subjected to an intraperitoneal glucose tolerance test. A third cohort of C57BL/6 mice was exposed to a cup regimen that included a component of massage and was subjected to tests of anxiety-like behavior, glucose homeostasis, and corticosterone secretion. We found that the cup mice showed reduced anxiety-like behaviors in the EPM coupled with a reduction in blood glucose levels compared to mice handled by the tail-picked method. Additionally, cup mice on the high fat diet exhibited improved glucose tolerance compared to tail-picked controls. Finally, we found that the cup/massage group showed lower glucose levels following an overnight fast, and decreased anxiety-like behaviors associated with lower stress-induced plasma corticosterone concentration compared to tail-picked controls. These data demonstrate that application of handling methods that reduce anxiety-like behaviors in mice mitigates the confounding contribution of stress to interpretation of metabolic endpoints (such as glucose tolerance).
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH 45237, United States. Electronic address: ghosalsa@mail.uc.edu.
authors.forename: Sriparna
authors.initials: S
authors.lastname: Ghosal
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH 45237, United States.
authors.forename: Amanda
authors.initials: A
authors.lastname: Nunley
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH 45237, United States.
authors.forename: Parinaz
authors.initials: P
authors.lastname: Mahbod
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH 45237, United States.
authors.forename: Alfor G
authors.initials: AG
authors.lastname: Lewis
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH 45237, United States.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Smith
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH 45237, United States.
authors.forename: Jenny
authors.initials: J
authors.lastname: Tong
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH 45237, United States.
authors.forename: David A
authors.initials: DA
authors.lastname: D'Alessio
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH 45237, United States.
authors.forename: James P
authors.initials: JP
authors.lastname: Herman
mesh_terms: D000221:Adaptation, Ocular; D000704:Analysis of Variance; D000818:Animals; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism*; D015331:Cohort Studies; D003345:Corticosterone / Q000097:blood*; D005106:Exploratory Behavior / Q000502:physiology; D005215:Fasting / Q000378:metabolism; D005951:Glucose Tolerance Test; D006234:Handling, Psychological; D008297:Male; D008405:Massage / Q000379:methods; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D013315:Stress, Psychological / Q000378:metabolism* / Q000534:rehabilitation*
chemical_list: D001786:Blood Glucose; D003345:Corticosterone
keywords: Corticosterone; Elevated plus maze; Glucose tolerance test; Handling