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. 1996 Mar;117(5):938–942. doi: 10.1111/j.1476-5381.1996.tb15284.x

Altered thermoregulatory responses to clonidine in streptozotocin-diabetic rats.

J M O'Donnell 1, T Banyasz 1, T Kovacs 1
PMCID: PMC1909417  PMID: 8851514

Abstract

1. The effects of streptozotocin (STZ) treatment on alpha 2-adrenoceptor regulation of body temperature were studied by monitoring the response of colonic temperature to administration of clonidine. 2. A dose-dependent fall in colonic temperature occurred in control rats given clonidine challenge (0.05-2.0 mg kg-1, s.c.); this response was inhibited by prior administration of either yohimbine or idazoxan (2 mg kg-1, s.c.) but not by the peripherally-acting alpha 2-adrenoceptor antagonist L-659,066 (10 mg kg-1, s.c.). 3. In rats treated with STZ (65 mg kg-1, i.v.) administration of clonidine elicited a dose-independent hyperthermia (circa 1 degree C.); this effect was unaltered by prior administration of yohimbine or idazoxan. 4. Naloxone (5 mg kg-1, s.c.) elicited a small fall in temperature (< 1 degree C.) in both control and STZ-treated rats; naloxone pretreatment did not alter the temperature response to clonidine in either group. 5. Nicotinic acid (10 mg kg-1, s.c.) caused a similar small elevation in temperature in both groups. 6. Administration of replacement insulin to STZ-treated rats maintained weight gain and low blood glucose while the thermoregulatory response to clonidine slowly reverted to normal. 7. These results show that altered central temperature control is an element of the generalised abnormality of alpha 2-receptor function induced by STZ.

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Selected References

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  1. Allard W. J., Vicario P. P., Saperstein R., Slater E. E., Strout H. V. The function but not the expression of rat liver inhibitory guanine nucleotide binding protein is altered in streptozotocin-induced diabetes. Endocrinology. 1991 Jul;129(1):169–175. doi: 10.1210/endo-129-1-169. [DOI] [PubMed] [Google Scholar]
  2. Bellush L. L., Henley W. N. Altered responses to environmental stress in streptozotocin-diabetic rats. Physiol Behav. 1990 Feb;47(2):231–238. doi: 10.1016/0031-9384(90)90136-r. [DOI] [PubMed] [Google Scholar]
  3. Bill D. J., Hughes I. E., Stephens R. J. The thermogenic actions of alpha 2-adrenoceptor agonists in reserpinized mice are mediated via a central postsynaptic alpha 2-adrenoceptor mechanism. Br J Pharmacol. 1989 Jan;96(1):133–143. doi: 10.1111/j.1476-5381.1989.tb11793.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Buccafusco J. J. Neuropharmacologic and behavioral actions of clonidine: interactions with central neurotransmitters. Int Rev Neurobiol. 1992;33:55–107. doi: 10.1016/s0074-7742(08)60691-1. [DOI] [PubMed] [Google Scholar]
  5. Chu P. C., Lin M. T., Shian L. R., Leu S. Y. Alterations in physiologic functions and in brain monoamine content in streptozocin-diabetic rats. Diabetes. 1986 Apr;35(4):481–485. doi: 10.2337/diab.35.4.481. [DOI] [PubMed] [Google Scholar]
  6. Clineschmidt B. V., Pettibone D. J., Lotti V. J., Hucker H. B., Sweeney B. M., Reiss D. R., Lis E. V., Huff J. R., Vacca J. A peripherally acting alpha-2 adrenoceptor antagonist: L-659,066. J Pharmacol Exp Ther. 1988 Apr;245(1):32–40. [PubMed] [Google Scholar]
  7. Guo T. Z., Maze B., Maze M. Attenuation of central alpha 2 adrenergic action in diabetic rats. Pharmacol Biochem Behav. 1991 Jun;39(2):383–387. doi: 10.1016/0091-3057(91)90196-9. [DOI] [PubMed] [Google Scholar]
  8. Kilgour R. D., Williams P. A. Impaired cardiovascular responsiveness to an acute cold wind stress in streptozotocin-diabetic rats. Comp Biochem Physiol Comp Physiol. 1994 Mar;107(3):537–543. doi: 10.1016/0300-9629(94)90037-x. [DOI] [PubMed] [Google Scholar]
  9. Lacković Z., Salković M., Kuci Z., Relja M. Effect of long-lasting diabetes mellitus on rat and human brain monoamines. J Neurochem. 1990 Jan;54(1):143–147. doi: 10.1111/j.1471-4159.1990.tb13294.x. [DOI] [PubMed] [Google Scholar]
  10. Leedom L. J., Meehan W. P. The psychoneuroendocrinology of diabetes mellitus in rodents. Psychoneuroendocrinology. 1989;14(4):275–294. doi: 10.1016/0306-4530(89)90030-9. [DOI] [PubMed] [Google Scholar]
  11. Livingston A., Low J., Morris B. Effects of clonidine and xylazine on body temperature in the rat. Br J Pharmacol. 1984 Jan;81(1):189–193. doi: 10.1111/j.1476-5381.1984.tb10760.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Locatelli V., Miyoshi H., Bestetti G., Rossi G. L., Müller E. E. Effect of growth hormone-releasing stimuli in streptozotocin diabetic rats. Brain Res. 1985 Aug 19;341(1):35–40. doi: 10.1016/0006-8993(85)91469-6. [DOI] [PubMed] [Google Scholar]
  13. MacKenzie R. G., Trulson M. E. Reduced sensitivity to L-tryptophan and p-chloroamphetamine in streptozotocin-diabetic rats. J Pharm Pharmacol. 1978 Feb;30(2):131–132. doi: 10.1111/j.2042-7158.1978.tb13182.x. [DOI] [PubMed] [Google Scholar]
  14. McCall A. L. The impact of diabetes on the CNS. Diabetes. 1992 May;41(5):557–570. doi: 10.2337/diab.41.5.557. [DOI] [PubMed] [Google Scholar]
  15. Mooradian A. D. Diabetic complications of the central nervous system. Endocr Rev. 1988 Aug;9(3):346–356. doi: 10.1210/edrv-9-3-346. [DOI] [PubMed] [Google Scholar]
  16. Oliver E. H., Sartin J. L., Dieberg G., Rahe C. H., Marple D. N., Kemppainen R. J. Effects of acute insulin deficiency on catecholamine and indoleamine content and catecholamine turnover in microdissected hypothalamic nuclei in streptozotocin-diabetic rats. Acta Endocrinol (Copenh) 1989 Mar;120(3):343–350. doi: 10.1530/acta.0.1200343. [DOI] [PubMed] [Google Scholar]
  17. Quan N., Xin L., Ungar A. L., Blatteis C. M. Preoptic norepinephrine-induced hypothermia is mediated by alpha 2-adrenoceptors. Am J Physiol. 1992 Mar;262(3 Pt 2):R407–R411. doi: 10.1152/ajpregu.1992.262.3.R407. [DOI] [PubMed] [Google Scholar]
  18. Ramabadran K., Bansinath M., Turndorf H., Puig M. M. Streptozotocin-diabetes attenuates alpha 2-adrenoceptor agonist-induced delay in small intestinal transit in mice. J Auton Pharmacol. 1990 Jun;10(3):163–171. doi: 10.1111/j.1474-8673.1990.tb00015.x. [DOI] [PubMed] [Google Scholar]
  19. Romanovsky A. A., Shido O., Ungar A. L., Blatteis C. M. Genesis of biphasic thermal response to intrapreoptically microinjected clonidine. Brain Res Bull. 1993;31(5):509–513. doi: 10.1016/0361-9230(93)90117-t. [DOI] [PubMed] [Google Scholar]
  20. Rowland N., Joyce J. N., Bellush L. L. Stereotyped behavior and diabetes mellitus in rats: reduced behavioral effects of amphetamine and apomorphine and reduced in vivo brain binding of [3H]spiroperidol. Behav Neurosci. 1985 Oct;99(5):831–841. doi: 10.1037//0735-7044.99.5.831. [DOI] [PubMed] [Google Scholar]
  21. Ryan C. M. Neurobehavioral complications of type I diabetes. Examination of possible risk factors. Diabetes Care. 1988 Jan;11(1):86–93. doi: 10.2337/diacare.11.1.86. [DOI] [PubMed] [Google Scholar]
  22. Shimizu H. Alteration in hypothalamic monoamine metabolism of freely moving diabetic rat. Neurosci Lett. 1991 Oct 14;131(2):225–227. doi: 10.1016/0304-3940(91)90619-5. [DOI] [PubMed] [Google Scholar]
  23. Simon G. S., Dewey W. L. Narcotics and diabetes. I. The effects of streptozotocin-induced diabetes on the antinociceptive potency of morphine. J Pharmacol Exp Ther. 1981 Aug;218(2):318–323. [PubMed] [Google Scholar]
  24. Zacny E. The role of alpha 2-adrenoceptors in the hypothermic effect of clonidine in the rat. J Pharm Pharmacol. 1982 Jul;34(7):455–456. doi: 10.1111/j.2042-7158.1982.tb04758.x. [DOI] [PubMed] [Google Scholar]

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