Abstract
1.We studied the effect of isolation stress in 3- and 12-month-old rats individually housed in metabolic cages for 7 days. Urine (24 hr) was collected daily from one group of animals of each age. The other group was tested in an open field and on a hot plate on days 1 and 7.
2.Total deambulation in the open-field test was lower in young than in older rats both on day 1 (54.7 ± 9.9 vs 80 ± 8.9 crossings/session; P < 0.04) and on day 7 (21 ± 9 vs 48 ± 7 crossings per session; P < 0.04) and decreased significantly in the two groups when tested on day 7 (P < 0.03). Latency to paw-licking in the hot-plate test was longer in young than in older animals on day 1 (14 ± 2 vs 8 ± 4 sec; P < 0.05) but was similar in the two groups on day 7.
3.Urinary excretions of norepinephrine (NE) and epinephrine (E) were determined by HPLC with electrochemical detection. Urinary NE in day 1 was similar in young and older animals (2627 ± 828 vs 3069 ± 598 ng/24 hr). In young animals NE excretion decreased along the study and was significantly (P < 0.02) lower than on day 1 during the last 3 days of the study. Conversely, in older animals urinary excretion of NE remained similar throughout the study. On day 7 urinary excretion of NE in older animals was about two fold that in young rats. Urinary E was similar in young and older rats (341 ± 127 vs 532 ± 256 ng/24 hr) on day 1 and showed a tendency to increase throughout the study.
4.Urinary monoamine oxidase inhibitory (IMAO) activity was determined by testing the ability of urine extracts to inhibit rat liver MAO activity in vitro and was higher in young than in older animals throughout the study (day 1, 54.8 ± 4.2 vs 25.1 ± 5.1%; P < 0.02). In young rats excretion of IMAO was significantly higher during the last 3 days of the study than on day 1 (P < 0.05). In older animals urinary IMAO showed a tendency to increase at the end of the study.
5.Isolation stress caused by housing rats in metabolic cages results in different behavioral and metabolic responses in young and older animals. Young animals exhibit a lower locomotor and analgesic response and excrete lower amounts of NE and higher IMAO activity in the urine than older rats. The metabolic and behavioral responses to isolation stress are highly dependent on the age of the animals tested. These results should be taken into consideration when designing experiments requiring the use of metabolic cages.
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REFERENCES
Armando, I., Glover, V., and Sandler, M. (1986). Distribution of endogenous benzodiazepine receptor ligand-monoamine oxidase inhibitory activity (tribulin) in tissues. Life Sci. 38:2063–2067.
Armando, I., Lemonie, A. P., Ferrini, M., Segura, E. T., and Barontini, M. (1989). Repeated (isolation) stress increases tribulin-like activity in the rat. Cell. Mol. Neurobiol. 9:115–122.
Armando, I., Levin, G., and Barontini, M. (1988). Stress increases endogenous benzodiazepine receptor ligand-monoamine oxidase inhibitory activity (tribulin) in rat tissues. J. Neural Transm. 71:29–37.
Avakian, E. V., Horvath, S. M., and Colburn, R. W. (1984). Influence of age and cold stress on plasma catecholamine levels in rats. J. Auton. Nerv. Syst. 10:127–133.
Battacharya, S. K., Glover, V., McIntyre, I., Oxenkrug, G., and Sandler, M. (1988). Stress causes an increase in endogenous monoamine oxidase inhibitor (tribulin) in rat brain. Neurosci. Lett. 92:218–221.
Bhattacharya, S. K., and Acharya, S. B. (1993). Further investigations on the anxiogenic effects of isatin. Biogenic Amines 9:453–463.
Bhattacharya, S. K., Chakrabarti, A., Sandler, M., and Glover, V. (1995). Rat brain monoamine oxidase A and B inhibitory (tribulin) activity during drug withdrawal anxiety. Neurosci. Lett. 199:103–106.
Bodnar, R. J., Kelly, D. D., Brutus, M., and Glusman, M. (1980). Stress-induced analgesia: Neural and hormonal determinants. Neurosci. Biobehav. Rev. 4:87–100.
Bures, J., Buresova, O., and Huston, J. (1976). Techniques and Basic Experiments for the Study of Brain and Behavior, Elsevier Scientific, Amsterdam.
Chiueh, C. C., Nespor, S. M., and Rapoport, S. I. (1980). Cardiovascular, sympathetic and adrenal cortical responsiveness of aged Fischer-344 rats to stres. Neurobiol. Aging 1:157–163.
Cizza, G., Gold, P. W., and Chrousos, G. P. (1995). Aging is associated in the 344/N Fischer rat with decreased stress responsitivity of central and peripheral catecholaminergic systems and impairment of the hypothalamic-pituitary-adrenal axis. Ann. N.Y. Acad. Sci. 771:491–511.
Doyle, A., Hucklebridge, F., Evans, P., and Clow, A. (1996). Urinary output of endogenous monoamine oxidase inhibitory activity is related to everyday stress. Life Sci. 58:1723–1730.
Eisenhofer, G., Goldstein, D. S., Stull, R., Keiser, H. R., Sunderland, T., Murphy, D. L., and Kopin, I. J., (1986). Simultaneous liquid chromatographic determination of 3,4 dihydroxyphenylglycol, catecholamines and 3,4 dihydroxyphenylalanine in plasma and their responses to inhibition of monoamine oxidase. Clin. Chem. 32:2030–2033.
Glover, V., and Sandler, M. (1993). Tribulin and isatin: An uptdate. In Yasuhara, H., Parvez, S., Oguchi, K., Sandler, M., and Nagatsu, T. (eds.), Monoamine Oxidase: Basic and Clinical Frontiers, VSP, Utrecht, pp. 61–71.
Glover, V., Reveley, M., and Sandler, M. (1980). A monoamine oxidase inhibitor in human urine. Biochem. Pharmacol. 29:467–470.
Glover, V., Bhattacharya, S. K., Sandler, M., and File, S. (1981). Benzodiazepine reduce stress-augmented increase in rat urine monoamine oxidase inhibitor. Nature 292:347–349.
Irwin, M., Hauger, R., and Brown, M. (1992). Central corticotropin-releasing hormone activates the sympathetic nervous system and reduces immune function: Increased responsitivity of the aged rat. Endocrinology 131:1047–1053.
Kopin, I. J. (1995). Definitions of stress and sympathetic neuronal responses. Ann. N.Y. Acad. Sci. 771:19–30.
Lemoine, A., Armando, I., Brun, J., Segura, E., and Barontini, M. (1990). Footshock affects heart and brain MAO and MAO inhibitory activity and open field behavior in rats. Pharmacol. Biochem. Behav. 36:85–88.
Mabry, T. R., Gold, P. E., and McCarty, R. (1995). Age-related changes in plasma catecholamine responses to chronic intermittent stress. Physiol. Behav. 58:49–56.
Mader, S. L., Downing, C. L., and Van Lunteren, E. (1991). Effect of age and hypoxia on beta-adrenergic receptors in rat heart. J. Appl. Physiol. 71(6):2094–2098.
Medvedev, A., Gorkin, V., Fedotova, I., Semiokhina, A., Glover, V., and Sandler, M. (1992). Increase of brain endogenous monoamine oxidase inhibitory activity (tribulin) in experimental audiogenic seizures in rats: Evidence for a monoamine oxidase A inhibitory component. Biochem. Pharmacol. 44:1209–1210.
Michalikova, S. H., Balazova, D., Jezova, D., and Kvetnansky, R. (1990). Changes in circulating catecholamines levels in old rats under basal conditions and during stress. Bratisl. Lek. Listry 91:689–693.
Royce, J. R. (1977). On the construct validity of open-field measures. Psychol. Bull. 84:1098–1106.
Sandler, M. (1982). The emergence of tribulin. Trends Pharm. Sci. 3:471–472.
Ziegler, M. G., Lake, C. R., and Kopin, I. J. (1976). Plasma noradrenaline increases with aging. Nature 261:333–335.
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Gil, M.C., Aguirre, J.A., Lemoine, A.P. et al. Influence of Age on Stress Responses to Metabolic Cage Housing in Rats. Cell Mol Neurobiol 19, 625–633 (1999). https://doi.org/10.1023/A:1006984402291
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DOI: https://doi.org/10.1023/A:1006984402291