Plasma corticosterone (CORT) measures are a common procedure to detect stress responses in rodents. However, the procedure is invasive and can influence CORT levels, making it less than ideal for monitoring CORT circadian rhythms. In the current paper, we examined the applicability of a non-invasive fecal CORT metabolite measure to assess the circadian rhythm. We compared fecal CORT metabolite levels to circulating CORT levels, and analyzed change in the fecal circadian rhythm following an acute stressor (i.e. blood sampling by tail veil catheter). Fecal and blood samples were collected from male adolescent rats and analyzed for CORT metabolites and circulating CORT respectively. Fecal samples were collected hourly for 24 h before and after blood draw. On average, peak fecal CORT metabolite values occurred 7-9 h after the plasma CORT peak and time-matched fecal CORT values were well correlated with plasma CORT. As a result of the rapid blood draw, fecal production and CORT levels were altered the next day. These results indicate fecal CORT metabolite measures can be used to assess conditions that disrupt the circadian CORT rhythm, and provide a method to measure long-term changes in CORT production. This can benefit research that requires long-term glucocorticoid assessment (e.g. stress mechanisms underlying health).

Brookhaven National Laboratory Medical Department Upton NY USA

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Bamberg E, Palme R, Meingassner JG. Excretion of corticosteroid metabolites in urine and faeces of rats. Lab Anim. 2001;35:307–14. PubMed

Brown LL, Siegel H, Etgen AM. Global sex differences in stress-induced activation of cerebral metabolism revealed by 2-deoxyglucose autoradiography. Horm Behav. 1996;30:611–7. PubMed

Cavigelli SA, Guhad FA, Ceballos RM, Whetzel CA, Nevalainen T, Lang CM, Klein LC. Fecal corticoid metabolites in aged male and female rats after husbandry-related disturbances in the colony room. J Am Assoc Lab Anim Sci. 2006;45:17–21. PubMed

Cavigelli SA, Monfort SL, Whitney TK, Mechref YS, Novotny M, McClintock MK. Frequent serial fecal corticoid measures from rats reflect circadian and ovarian corticosterone rhythms. J Endocrinol. 2005;184:153–63. PubMed

Deuschle M, Schweiger U, Weber B, Gotthardt U, Korner A, Schmider J, Standhardt H, Lammers CH, Heuser I. Diurnal activity and pulsatility of the hypothalamus-pituitary-adrenal system in male depressed patients and healthy controls. J Clin Endocrinol Metab. 1997;82:234–8. PubMed

Duncan GE, Johnson KB, Breese GR. Topographic patterns of brain activity in response to swim stress: assessment by 2-deoxyglucose uptake and expression of Fos-like immunoreactivity. J Neurosci. 1993;13:3932–43. PubMed PMC

Eriksson E, Royo F, Lyberg K, Carlsson HE, Hau J. Effect of metabolic cage housing on immunoglobulin A and corticosterone excretion in faeces and urine of young male rats. Exp Physiol. 2004;89:427–33. PubMed

Fluttert M, Dalm S, Oitzl MS. A refined method for sequential blood sampling by tail incision in rats. Lab Anim. 2000;34:372–8. PubMed

Gartner K, Buttner D, Dohler K, Friedel R, Lindena J, Trautschold I. Stress response of rats to handling and experimental procedures. Lab Anim. 1980;14:267–74. PubMed

Haemisch A, Guerra G, Furkert J. Adaptation of corticosterone-but not beta-endorphin-secretion to repeated blood sampling in rats. Lab Anim. 1999;33:185–91. PubMed

Harris RB, GU H, Mitchell TD, Endale L, Russo M, Ryan DH. Increased glucocorticoid response to a novel stress in rats that have been restrained. Physiol Behav. 2004;81:557–68. PubMed

Kishibayashi N, Yokoyama T, Karasawa A. Enhancement of defecation and distal colonic motor activity by KW-5092, a novel gastroprokinetic agent, in rats. Arch Int Pharmacodyn Ther. 1995;329:295–306. PubMed

Macey DJ, Rice WN, Freedland CS, Whitlow CT, Porrino LJ. Patterns of functional activity associated with cocaine self-administration in the rat change over time. Psychopharmacology (Berl) 2004;172:384–92. PubMed

Mantsch JR, Yuferov V, Mathieu-Kia AM, Ho A, Kreek MJ. Neuroendocrine alterations in a high-dose, extended-access rat self-administration model of escalating cocaine use. Psychoneuroendocrinology. 2003;28:836–62. PubMed

Mormede P, Andanson S, Auperin B, Beerda B, Guemene D, Malmkvist J, Manteca X, Manteuffel G, Prunet P, van Reenen CG, Richard S, Veissier I. Exploration of the hypothalamic-pituitary-adrenal function as a tool to evaluate animal welfare. Physiol Behav. 2007;92:317–39. PubMed

Pace TW, Spencer RL. Disruption of mineralocorticoid receptor function increases corticosterone responding to a mild, but not moderate, psychological stressor. Am J Physiol Endocrinol Metab. 2005;288:E1082–8. PubMed

Piazza PV, Le Moal M. The role of stress in drug self-administration. Trends Pharmacol Sci. 1998;19:67–74. PubMed

Porrino LJ, Lucignani G. Different patterns of local brain energy metabolism associated with high and low doses of methylphenidate. Relevance to its action in hyperactive children. Biol Psychiatry. 1987;22:126–38. PubMed

Porrino LJ, Lyons D, Miller MD, Smith HR, Friedman DP, Daunais JB, Nader MA. Metabolic mapping of the effects of cocaine during the initial phases of self-administration in the nonhuman primate. J Neurosci. 2002;22:7687–94. PubMed PMC

Royo F, Bjork N, Carlsson HE, Mayo S, Hau J. Impact of chronic catheterization and automated blood sampling (Accusampler) on serum corticosterone and fecal immunoreactive corticosterone metabolites and immunoglobulin A in male rats. J Endocrinol. 2004;180:145–53. PubMed

Sadoyama G, Gontijo Filho PP. Comparison between the jugular and subclavian vein as insertion site for central venous catheters: microbiological aspects and risk factors for colonization and infection. Braz J Infect Dis. 2003;7:142–8. PubMed

Sharp JL, Zammit TG, Azar TA, Lawson DM. Stress-like responses to common procedures in male rats housed alone or with other rats. Contemp Top Lab Anim Sci. 2002;41:8–14. PubMed

Sinha R. How does stress increase risk of drug abuse and relapse? Psychopharmacology (Berl) 2001;158:343–59. PubMed

Touma C, Palme R. Measuring fecal glucocorticoid metabolites in mammals and birds: the importance of validation. Ann N Y Acad Sci. 2005;1046:54–74. PubMed

Touma C, Sachser N, Mostl E, Palme R. Effects of sex and time of day on metabolism and excretion of corticosterone in urine and feces of mice. Gen Comp Endocrinol. 2003;130:267–78. PubMed

Tuli JS, Smith JA, Morton DB. Corticosterone, adrenal and spleen weight in mice after tail bleeding, and its effect on nearby animals. Lab Anim. 1995;29:90–5. PubMed

Vahl TP, Ulrich-Lai YM, Ostrander MM, Dolgas CM, Elfers EE, Seeley RJ, D’Alessio DA, Herman JP. Comparative analysis of ACTH and corticosterone sampling methods in rats. Am J Physiol Endocrinol Metab. 2005;289:E823–8. PubMed

Whitlow CT, Freedland CS, Porrino LJ. Metabolic mapping of the time-dependent effects of delta 9-tetrahydrocannabinol administration in the rat. Psychopharmacology (Berl) 2002;161:129–36. PubMed

Williams-Hemby L, Grant KA, Gatto GJ, Porrino LJ. Metabolic mapping of the effects of chronic voluntary ethanol consumption in rats. Pharmacol Biochem Behav. 1996;54:415–23. PubMed

Windle RJ, Wood SA, Lightman SL, Ingram CD. The pulsatile characteristics of hypothalamo-pituitary-adrenal activity in female Lewis and Fischer 344 rats and its relationship to differential stress responses. Endocrinology. 1998;139:4044–52. PubMed

Wright-Williams SL, Courade JP, Richardson CA, Roughan JV, Flecknell PA. Effects of vasectomy surgery and meloxicam treatment on faecal corticosterone levels and behaviour in two strains of laboratory mouse. Pain. 2006;130:108–18. PubMed

Yang J, Maarek JM, Holschneider DP. In vivo quantitative assessment of catheter patency in rats. Lab Anim. 2005;39:259–68. PubMed PMC