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. 1985 Sep;86(1):209–216. doi: 10.1111/j.1476-5381.1985.tb09451.x

The 5-HT1 receptor agonist RU-24969 decreases 5-hydroxytryptamine (5-HT) release and metabolism in the rat frontal cortex in vitro and in vivo.

M P Brazell, C A Marsden, A P Nisbet, C Routledge
PMCID: PMC1916850  PMID: 2413936

Abstract

K+-stimulated release of [3H]-5-hydroxytryptamine ( [3H]-5-HT) from rat frontal cortex slices was decreased by the 5-HT receptor agonists 5-methoxy-n1N-dimethyltryptamine and 5-methoxy-3(1,2,3,6,-tetrahydro-4-pyrindinyl)-1H-indole (RU-24969) (1 X 10(-5)M). RU-24969 (10 mg kg-1, i.p.) decreased extracellular 5-HT and its metabolite 5-hydroxyindoleacetic acid measured in vivo by use of intracerebral dialysis combined with high performance liquid chromatography and electrochemical detection. The decrease in extracellular 5-hydroxyindoleacetic acid in vivo after RU-24969 (10 mg kg-1, i.p.) was also observed by in vivo voltammetry. The non-selective 5-HT antagonist metergoline prevented the RU-24969-induced decrease in 5-HT release and metabolism in vivo while the 5-HT2 receptor antagonist R-55669 (ritanserin) did not. The results support the view that RU-24969 stimulates a 5-HT1 receptor that is involved in the autoregulation of 5-HT release and metabolism.

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Selected References

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

  1. Baumann P. A., Waldmeier P. C. Negative feedback control of serotonin release in vivo: comparison of 5-hydroxyindolacetic acid levels measured by voltammetry in conscious rats and by biochemical techniques. Neuroscience. 1984 Jan;11(1):195–204. doi: 10.1016/0306-4522(84)90223-9. [DOI] [PubMed] [Google Scholar]
  2. Bennett G. W., Sharp T., Marsden C. A., Parker T. L. A manually-operated brain tissue slicer suitable for neurotransmitter release studies. J Neurosci Methods. 1983 Feb;7(2):107–115. doi: 10.1016/0165-0270(83)90073-0. [DOI] [PubMed] [Google Scholar]
  3. Cespuglio R., Faradji H., Riou F., Buda M., Gonon F., Pujol J. F., Jouvet M. Differential pulse voltammetry in brain tissue. II. Detection of 5-hydroxyindoleacetic acid in the rat striatum. Brain Res. 1981 Nov 2;223(2):299–311. doi: 10.1016/0006-8993(81)91143-4. [DOI] [PubMed] [Google Scholar]
  4. Crespi F., Sharp T., Maidment N., Marsden C. Differential pulse voltammetry in vivo--evidence that uric acid contributes to the indole oxidation peak. Neurosci Lett. 1983 Dec 30;43(2-3):203–207. doi: 10.1016/0304-3940(83)90188-x. [DOI] [PubMed] [Google Scholar]
  5. Engel G., Göthert M., Müller-Schweinitzer E., Schlicker E., Sistonen L., Stadler P. A. Evidence for common pharmacological properties of [3H]5-hydroxytryptamine binding sites, presynaptic 5-hydroxytryptamine autoreceptors in CNS and inhibitory presynaptic 5-hydroxytryptamine receptors on sympathetic nerves. Naunyn Schmiedebergs Arch Pharmacol. 1983 Sep;324(2):116–124. doi: 10.1007/BF00497016. [DOI] [PubMed] [Google Scholar]
  6. Euvrard C., Boissier J. R. Biochemical assessment of the central 5-HT agonist activity of RU 24969 (a piperidinyl indole). Eur J Pharmacol. 1980 Apr 11;63(1):65–72. doi: 10.1016/0014-2999(80)90117-x. [DOI] [PubMed] [Google Scholar]
  7. Gozlan H., El Mestikawy S., Pichat L., Glowinski J., Hamon M. Identification of presynaptic serotonin autoreceptors using a new ligand: 3H-PAT. Nature. 1983 Sep 8;305(5930):140–142. doi: 10.1038/305140a0. [DOI] [PubMed] [Google Scholar]
  8. Green A. R., Guy A. P., Gardner C. R. The behavioural effects of RU 24969, a suggested 5-HT1 receptor agonist in rodents and the effect on the behaviour of treatment with antidepressants. Neuropharmacology. 1984 Jun;23(6):655–661. doi: 10.1016/0028-3908(84)90147-3. [DOI] [PubMed] [Google Scholar]
  9. Göthert M. Serotonin-receptor-mediated modulation of Ca2+-dependent 5-hydroxytryptamine release from neurones of the rat brain cortex. Naunyn Schmiedebergs Arch Pharmacol. 1980 Nov;314(3):223–230. doi: 10.1007/BF00498543. [DOI] [PubMed] [Google Scholar]
  10. Middlemiss D. N. 8-Hydroxy-2-(di-n-propylamino) tetralin is devoid of activity at the 5-hydroxytryptamine autoreceptor in rat brain. Implications for the proposed link between the autoreceptor and the [3H] 5-HT recognition site. Naunyn Schmiedebergs Arch Pharmacol. 1984 Aug;327(1):18–22. doi: 10.1007/BF00504986. [DOI] [PubMed] [Google Scholar]
  11. Middlemiss D. N. Stereoselective blockade at [3H]5-HT binding sites and at the 5-HT autoreceptor by propranolol. Eur J Pharmacol. 1984 Jun 1;101(3-4):289–293. doi: 10.1016/0014-2999(84)90173-0. [DOI] [PubMed] [Google Scholar]
  12. Schlicker E., Göthert M. Antagonistic properties of quipazine at presynaptic serotonin receptors and alpha-adrenoceptors in rat brain cortex slices. Naunyn Schmiedebergs Arch Pharmacol. 1981 Nov;317(3):204–208. doi: 10.1007/BF00503817. [DOI] [PubMed] [Google Scholar]
  13. Sharp T., Maidment N. T., Brazell M. P., Zetterström T., Ungerstedt U., Bennett G. W., Marsden C. A. Changes in monoamine metabolites measured by simultaneous in vivo differential pulse voltammetry and intracerebral dialysis. Neuroscience. 1984 Aug;12(4):1213–1221. doi: 10.1016/0306-4522(84)90015-0. [DOI] [PubMed] [Google Scholar]
  14. Zetterström T., Sharp T., Marsden C. A., Ungerstedt U. In vivo measurement of dopamine and its metabolites by intracerebral dialysis: changes after d-amphetamine. J Neurochem. 1983 Dec;41(6):1769–1773. doi: 10.1111/j.1471-4159.1983.tb00893.x. [DOI] [PubMed] [Google Scholar]

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