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







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