Skip to main content
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1991 Sep;104(1):105–112. doi: 10.1111/j.1476-5381.1991.tb12392.x

Effects of 5-HT uptake inhibitors, agonists and antagonists on the burying of harmless objects by mice; a putative test for anxiolytic agents.

K Njung'e 1, S L Handley 1
PMCID: PMC1908295  PMID: 1686200

Abstract

1. The effects of 5-hydroxytryptamine (5-HT) uptake inhibitors, agonists and antagonists have been evaluated on mouse marble-burying behaviour, a putative test for anxiolytic agents. The high levels of locomotor activity occurring on first exposure to a circular runway (runway were used as a separate test of non-specific drug effects. 2. Fluvoxamine, zimeldine, indalpine and citalopram dose-dependently inhibited burying without affecting runway activity. 5-Hydroxytryptophan (5-HTP, with carbidopa), 5-methoxy-N,N-dimethyltryptamine, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OHDPAT), buspirione, gepirone and ipsapirone reduced burying only at doses reducing runway activity. RU 24969 increased runway activity at all effective doses. 1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane (DOI), 1,-(3-trifluoromethylphenyl) piperazine (TFMPP) and 1-(3-chlorophenyl)-piperazine (mCPP) potently and differentially reduced burying at doses below those affecting runway activity. 3. 5-HT antagonists only reduced burying at high doses which also reduced runway activity. Burying inhibition by DOI was antagonized by ritanserin, ICI 169,369 and cyproheptadine but not by pindolol or a low (0.25 mg kg-1) dose of metergoline. Burying inhibition by mCPP was not altered by any of these agents except that it was potentiated by pindolol 5 mg kg-1. 4. Zimeldine burying inhibition was potentiated by ritanserine, ICI 169,369, ICS 205-930, cyproheptadine and pindolol. Runway activity was not affected by these drug combinations. 5. Zimeldine was administered in drinking water at a dose of 10 mg kg-1 daily for 21 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
105

Selected References

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

  1. Alifimoff J. K., Firestone L. L., Miller K. W. Anaesthetic potencies of primary alkanols: implications for the molecular dimensions of the anaesthetic site. Br J Pharmacol. 1989 Jan;96(1):9–16. doi: 10.1111/j.1476-5381.1989.tb11777.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Arnt J., Hyttel J. Facilitation of 8-OHDPAT-induced forepaw treading of rats by the 5-HT2 agonist DOI. Eur J Pharmacol. 1989 Feb 14;161(1):45–51. doi: 10.1016/0014-2999(89)90178-7. [DOI] [PubMed] [Google Scholar]
  3. Auerbach S. B., Kamalakannan N., Rutter J. J. TFMPP and RU24969 enhance serotonin release from rat hippocampus. Eur J Pharmacol. 1990 Nov 6;190(1-2):51–57. doi: 10.1016/0014-2999(90)94111-a. [DOI] [PubMed] [Google Scholar]
  4. Backus L. I., Sharp T., Grahame-Smith D. G. Behavioural evidence for a functional interaction between central 5-HT2 and 5-HT1A receptors. Br J Pharmacol. 1990 Aug;100(4):793–799. doi: 10.1111/j.1476-5381.1990.tb14094.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Broekkamp C. L., Berendsen H. H., Jenck F., Van Delft A. M. Animal models for anxiety and response to serotonergic drugs. Psychopathology. 1989;22 (Suppl 1):2–12. doi: 10.1159/000284620. [DOI] [PubMed] [Google Scholar]
  6. Darmani N. A., Martin B. R., Pandey U., Glennon R. A. Pharmacological characterization of ear-scratch response in mice as a behavioral model for selective 5-HT2-receptor agonists and evidence for 5-HT1B- and 5-HT2-receptor interactions. Pharmacol Biochem Behav. 1990 Sep;37(1):95–99. doi: 10.1016/0091-3057(90)90047-l. [DOI] [PubMed] [Google Scholar]
  7. Garattini S., Mennini T., Samanin R. Reduction of food intake by manipulation of central serotonin. Current experimental results. Br J Psychiatry Suppl. 1989 Dec;(8):41–51. [PubMed] [Google Scholar]
  8. Goodwin G. M., Green A. R. A behavioural and biochemical study in mice and rats of putative selective agonists and antagonists for 5-HT1 and 5-HT2 receptors. Br J Pharmacol. 1985 Mar;84(3):743–753. doi: 10.1111/j.1476-5381.1985.tb16157.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hoyer D. Molecular pharmacology and biology of 5-HT1C receptors. Trends Pharmacol Sci. 1988 Mar;9(3):89–94. doi: 10.1016/0165-6147(88)90174-5. [DOI] [PubMed] [Google Scholar]
  10. Hoyer D., Waeber C., Schoeffter P., Palacios J. M., Dravid A. 5-HT1C receptor-mediated stimulation of inositol phosphate production in pig choroid plexus. A pharmacological characterization. Naunyn Schmiedebergs Arch Pharmacol. 1989 Mar;339(3):252–258. doi: 10.1007/BF00173573. [DOI] [PubMed] [Google Scholar]
  11. Kennett G. A., Whitton P., Shah K., Curzon G. Anxiogenic-like effects of mCPP and TFMPP in animal models are opposed by 5-HT1C receptor antagonists. Eur J Pharmacol. 1989 May 30;164(3):445–454. doi: 10.1016/0014-2999(89)90252-5. [DOI] [PubMed] [Google Scholar]
  12. Njung'e K., Handley S. L. Evaluation of marble-burying behavior as a model of anxiety. Pharmacol Biochem Behav. 1991 Jan;38(1):63–67. doi: 10.1016/0091-3057(91)90590-x. [DOI] [PubMed] [Google Scholar]
  13. Nutt D. J., Glue P. Clinical pharmacology of anxiolytics and antidepressants: a psychopharmacological perspective. Pharmacol Ther. 1989;44(3):309–334. doi: 10.1016/0163-7258(89)90006-5. [DOI] [PubMed] [Google Scholar]
  14. Pettibone D. J., Williams M. Serotonin-releasing effects of substituted piperazines in vitro. Biochem Pharmacol. 1984 May 1;33(9):1531–1535. doi: 10.1016/0006-2952(84)90424-6. [DOI] [PubMed] [Google Scholar]
  15. Poling A., Cleary J., Monaghan M. Burying by rats in response to aversive and nonaversive stimuli. J Exp Anal Behav. 1981 Jan;35(1):31–44. doi: 10.1901/jeab.1981.35-31. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Treit D. Animal models for the study of anti-anxiety agents: a review. Neurosci Biobehav Rev. 1985 Summer;9(2):203–222. doi: 10.1016/0149-7634(85)90046-6. [DOI] [PubMed] [Google Scholar]
  17. Winslow J. T., Insel T. R. Neurobiology of obsessive compulsive disorder: a possible role for serotonin. J Clin Psychiatry. 1990 Aug;51 (Suppl):27–58. [PubMed] [Google Scholar]

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

RESOURCES