Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1991 Sep;104(1):258–262. doi: 10.1111/j.1476-5381.1991.tb12416.x

The effects of idazoxan and other alpha 2-adrenoceptor antagonists on food and water intake in the rat.

H C Jackson 1, I J Griffin 1, D J Nutt 1
PMCID: PMC1908278  PMID: 1686207

Abstract

1. Idazoxan (1, 3, 10 mg kg-1, i.p.) produced a significant increase in food and water intake in freely feeding rats during the daylight phase. 2. The more selective and specific alpha 2-adrenoceptor antagonists, RX811059 (0.3, 1, 3 mg kg-1, i.p.) and RX821002 (0.3, 1, 3 mg kg-1, i.p.), did not produce hyperphagia in rats, however, the highest dose produced a significant increase in water intake. 3. The peripherally acting alpha 2-adrenoceptor antagonist, L-659,066 (1, 3, 10 mg kg-1, i.p.), did not affect food intake in the 4 h following injection, but the highest dose (10 mg kg-1), produced a large increase in water intake. 4. These results indicate that alpha 2-adrenoceptor antagonists may increase water intake by a peripherally mediated mechanism. 5. The lack of effect RX811059 and RX821002 on food intake contrasts with the large dose-related increases induced by idazoxan and suggests that the hyperphagic effects of idazoxan are not due to alpha 2-adrenoceptor blockade but may instead reflect its affinity for a non-adrenoceptor site, a property not shared by the other alpha 2-antagonists.

Full text

PDF
258

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Atkinson J., Kirchertz E. J., Peters-Haefeli L. Effect of peripheral clonidine on ingestive behavior. Physiol Behav. 1978 Jul;21(1):73–77. doi: 10.1016/0031-9384(78)90279-2. [DOI] [PubMed] [Google Scholar]
  2. Brown C. M., MacKinnon A. C., McGrath J. C., Spedding M., Kilpatrick A. T. Alpha 2-adrenoceptor subtypes and imidazoline-like binding sites in the rat brain. Br J Pharmacol. 1990 Apr;99(4):803–809. doi: 10.1111/j.1476-5381.1990.tb13010.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chapleo C. B., Myers P. L., Butler R. C., Davis J. A., Doxey J. C., Higgins S. D., Myers M., Roach A. G., Smith C. F., Stillings M. R. Alpha-adrenoreceptor reagents. 2. Effects of modification of the 1,4-benzodioxan ring system on alpha-adrenoreceptor activity. J Med Chem. 1984 May;27(5):570–576. doi: 10.1021/jm00371a003. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Dennis T., L'Heureux R., Carter C., Scatton B. Presynaptic alpha-2 adrenoceptors play a major role in the effects of idazoxan on cortical noradrenaline release (as measured by in vivo dialysis) in the rat. J Pharmacol Exp Ther. 1987 May;241(2):642–649. [PubMed] [Google Scholar]
  6. Dourish C. T., Hutson P. H., Curzon G. Low doses of the putative serotonin agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) elicit feeding in the rat. Psychopharmacology (Berl) 1985;86(1-2):197–204. doi: 10.1007/BF00431709. [DOI] [PubMed] [Google Scholar]
  7. Drew G. M., Gower A. J., Marriott A. S. Alpha 2-adrenoceptors mediate clonidine-induced sedation in the rat. Br J Pharmacol. 1979 Sep;67(1):133–141. [PMC free article] [PubMed] [Google Scholar]
  8. Freedman J. E., Aghajanian G. K. Idazoxan (RX 781094) selectively antagonizes alpha 2-adrenoceptors on rat central neurons. Eur J Pharmacol. 1984 Oct 15;105(3-4):265–272. doi: 10.1016/0014-2999(84)90618-6. [DOI] [PubMed] [Google Scholar]
  9. Fregly M. J., Kelleher D. L., Greenleaf J. E. Antidipsogenic effect of clonidine on angiotensin II-, hypertonic saline-, pilocarpine- and dehydration-induced water intakes. Brain Res Bull. 1981 Dec;7(6):661–664. doi: 10.1016/0361-9230(81)90114-3. [DOI] [PubMed] [Google Scholar]
  10. Fregly M. J., Rowland N. E., Greenleaf J. E. Effects of yohimbine and tolazoline on isoproterenol and angiotensin II-induced water intake in rats. Brain Res Bull. 1983 Jan;10(1):121–126. doi: 10.1016/0361-9230(83)90083-7. [DOI] [PubMed] [Google Scholar]
  11. Fuller L. M. The pharmacology of drinking behavior. Pharmacol Ther. 1984;24(2):179–206. doi: 10.1016/0163-7258(84)90034-2. [DOI] [PubMed] [Google Scholar]
  12. Gellai M. Modulation of vasopressin antidiuretic action by renal alpha 2-adrenoceptors. Am J Physiol. 1990 Jul;259(1 Pt 2):F1–F8. doi: 10.1152/ajprenal.1990.259.1.F1. [DOI] [PubMed] [Google Scholar]
  13. Goldman C. K., Marino L., Leibowitz S. F. Postsynaptic alpha 2-noradrenergic receptors mediate feeding induced by paraventricular nucleus injection of norepinephrine and clonidine. Eur J Pharmacol. 1985 Sep 10;115(1):11–19. doi: 10.1016/0014-2999(85)90578-3. [DOI] [PubMed] [Google Scholar]
  14. Goldstein J. M., Knobloch-Litwin L. C., Malick J. B. Behavioral evidence for beta-adrenoceptor subsensitivity after subacute antidepressant/alpha 2-adrenoceptor antagonist treatment. Naunyn Schmiedebergs Arch Pharmacol. 1985 Jun;329(4):355–358. doi: 10.1007/BF00496367. [DOI] [PubMed] [Google Scholar]
  15. Heal D. J., Philpot J., O'Shaughnessy K. M., Davies C. L. The influence of central noradrenergic function on 5-HT2-mediated head-twitch responses in mice: possible implications for the actions of antidepressant drugs. Psychopharmacology (Berl) 1986;89(4):414–420. doi: 10.1007/BF02412113. [DOI] [PubMed] [Google Scholar]
  16. Langin D., Lafontan M., Stillings M. R., Paris H. [3H]RX821002: a new tool for the identification of alpha 2A-adrenoceptors. Eur J Pharmacol. 1989 Aug 11;167(1):95–104. doi: 10.1016/0014-2999(89)90751-6. [DOI] [PubMed] [Google Scholar]
  17. Langin D., Paris H., Lafontan M. Binding of [3H]idazoxan and of its methoxy derivative [3H] RX821002 in human fat cells: [3H]idazoxan but not [3H] RX821002 labels additional non-alpha 2-adrenergic binding sites. Mol Pharmacol. 1990 Jun;37(6):876–885. [PubMed] [Google Scholar]
  18. Leenen F. H., McDonald R. H., Jr Effect of isoproterenol on blood pressure, plasma renin activity, and water intake in rats. Eur J Pharmacol. 1974 May;26(2):129–135. doi: 10.1016/0014-2999(74)90218-0. [DOI] [PubMed] [Google Scholar]
  19. Lehr D., Mallow J., Krukowski M. Copious drinking and simultaneous inhibition of urine flow elicited by beta-adrenergic stimulation and contrary effect of alpha-adrenergic stimulation. J Pharmacol Exp Ther. 1967 Oct;158(1):150–163. [PubMed] [Google Scholar]
  20. Lewis C. J., Havler M. E., Humphrey M. J., Lloyd-Jones J. G., McCleavy M. A., Muir N. C., Waltham K. The pharmacokinetics and metabolism of idazoxan in the rat. Xenobiotica. 1988 May;18(5):519–532. doi: 10.3109/00498258809041689. [DOI] [PubMed] [Google Scholar]
  21. Marsden C. A., Martin K. F. Involvement of 5-HT1A- and alpha 2-receptors in the decreased 5-hydroxytryptamine release and metabolism in rat suprachiasmatic nucleus after intravenous 8-hydroxy-2-(n-dipropylamino) tetralin. Br J Pharmacol. 1986 Oct;89(2):277–286. doi: 10.1111/j.1476-5381.1986.tb10257.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. McCabe J. T., DeBellis M., Leibowitz S. F. Clonidine-induced feeding: analysis of central sites of action and fiber projections mediating this response. Brain Res. 1984 Aug 20;309(1):85–104. doi: 10.1016/0006-8993(84)91013-8. [DOI] [PubMed] [Google Scholar]
  23. Michel M. C., Insel P. A. Are there multiple imidazoline binding sites? Trends Pharmacol Sci. 1989 Sep;10(9):342–344. doi: 10.1016/0165-6147(89)90002-3. [DOI] [PubMed] [Google Scholar]
  24. Pettinger W. A., Keeton T. K., Campbell W. B., Harper D. C. Evidence for a renal alpha-adrenergic receptor inhibiting renin release. Circ Res. 1976 May;38(5):338–346. doi: 10.1161/01.res.38.5.338. [DOI] [PubMed] [Google Scholar]
  25. Ramsay D. J. Beta-adrenergic thirst and its relation to the renin-angiotensin system. Fed Proc. 1978 Nov;37(13):2689–2693. [PubMed] [Google Scholar]
  26. Sanger D. J. An analysis of the effects of systemically administered clonidine on the food and water intake of rats. Br J Pharmacol. 1983 Jan;78(1):159–164. doi: 10.1111/j.1476-5381.1983.tb09376.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Tricklebank M. D., Forler C., Fozard J. R. The involvement of subtypes of the 5-HT1 receptor and of catecholaminergic systems in the behavioural response to 8-hydroxy-2-(di-n-propylamino)tetralin in the rat. Eur J Pharmacol. 1984 Nov 13;106(2):271–282. doi: 10.1016/0014-2999(84)90714-3. [DOI] [PubMed] [Google Scholar]
  28. Walter D. S., Flockhart I. R., Haynes M. J., Howlett D. R., Lane A. C., Burton R., Johnson J., Dettmar P. W. Effects of idazoxan on catecholamine systems in rat brain. Biochem Pharmacol. 1984 Aug 15;33(16):2553–2557. doi: 10.1016/0006-2952(84)90623-3. [DOI] [PubMed] [Google Scholar]
  29. limberger N., Starke K. Partial agonist effect of 2-[2-(1,4-benzodioxanyl)]-2-imidazoline (RX 781 094) at presynaptic alpha 2-adrenoceptors in rabbit ear artery. Naunyn Schmiedebergs Arch Pharmacol. 1983 Sep;324(1):75–78. doi: 10.1007/BF00647842. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES