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. 1992 Jul;106(3):524–532. doi: 10.1111/j.1476-5381.1992.tb14369.x

Pharmacological characteristics of 5-hydroxytryptamine autoreceptors in rat brain slices incorporating the dorsal raphe or the suprachiasmatic nucleus.

J J O'Connor 1, Z L Kruk 1
PMCID: PMC1907542  PMID: 1504738

Abstract

1. Changes in extracellular concentrations of 5-hydroxytryptamine elicited by electrical stimulation in rat brain slices containing the dorsal raphe nucleus and the suprachiasmatic nucleus were monitored with fast cyclic voltammetry. 2. Using pseudo single pulse stimulation (5 pulses applied at 100 Hz) we have shown that the release of 5-hydroxytryptamine in the dorsal raphe and the suprachiasmatic nucleus can be regulated by autoreceptors in both brain regions. 3. In the suprachiasmatic nucleus, 5-carboxamidotryptamine, RU24969, 1-(m-trifluoromethylphenyl) piperazine and sumatriptan caused a concentration-dependent inhibition of stimulated 5-hydroxytryptamine overflow in the range 1 x 10(-9) M to 3 x 10(-6) M. The actions of 5-carboxamidotryptamine and RU24969 were reversed competitively by methiothepin (10(-8) M to 10(-6) M); Schild plots revealed pKB values of 7.9 and 8.1. By contrast, ipsaparone and 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT) are not effective 5-hydroxytryptamine autoreceptor agonists in the suprachiasmatic nucleus. 4. Isamoltane (10(-6) M), the putative 5-HT1B receptor antagonist, blocked the responses to RU24969 (10(-6) M) and 1-(m-trifluoromethylphenyl)piperazine (10(-6) M) in the suprachiasmatic nucleus. 5. In the dorsal raphe nucleus, 8-OH-DPAT, ipsapirone, RU24969, 5-carboxamidotryptamine, and sumatriptan (all 1 x 10(-8) M to 3 x 10(-6) M) produced a concentration-dependent reduction in the stimulated release of 5-hydroxytryptamine. The maximum effect observed was less than that seen in the suprachiasmatic nucleus.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. ARUNLAKSHANA O., SCHILD H. O. Some quantitative uses of drug antagonists. Br J Pharmacol Chemother. 1959 Mar;14(1):48–58. doi: 10.1111/j.1476-5381.1959.tb00928.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bradley P. B., Engel G., Feniuk W., Fozard J. R., Humphrey P. P., Middlemiss D. N., Mylecharane E. J., Richardson B. P., Saxena P. R. Proposals for the classification and nomenclature of functional receptors for 5-hydroxytryptamine. Neuropharmacology. 1986 Jun;25(6):563–576. doi: 10.1016/0028-3908(86)90207-8. [DOI] [PubMed] [Google Scholar]
  3. Bull D. R., Palij P., Sheehan M. J., Millar J., Stamford J. A., Kruk Z. L., Humphrey P. P. Application of fast cyclic voltammetry to measurement of electrically evoked dopamine overflow from brain slices in vitro. J Neurosci Methods. 1990 Apr;32(1):37–44. doi: 10.1016/0165-0270(90)90069-r. [DOI] [PubMed] [Google Scholar]
  4. Bull D. R., Sheehan M. J. Presynaptic regulation of electrically evoked dopamine overflow in nucleus accumbens: a pharmacological study using fast cyclic voltammetry in vitro. Naunyn Schmiedebergs Arch Pharmacol. 1991 Mar;343(3):260–265. doi: 10.1007/BF00251124. [DOI] [PubMed] [Google Scholar]
  5. Cejna M., Agneter E., Drobny H., Valenta B., Singer E. A. Pulse-to-pulse modulation of transmitter release in the central nervous system. Basic and pharmacological aspects. Ann N Y Acad Sci. 1990;604:211–221. doi: 10.1111/j.1749-6632.1990.tb31995.x. [DOI] [PubMed] [Google Scholar]
  6. Dompert W. U., Glaser T., Traber J. 3H-TVX Q 7821: identification of 5-HT1 binding sites as target for a novel putative anxiolytic. Naunyn Schmiedebergs Arch Pharmacol. 1985 Feb;328(4):467–470. doi: 10.1007/BF00692918. [DOI] [PubMed] [Google Scholar]
  7. Dumuis A., Bouhelal R., Sebben M., Cory R., Bockaert J. A nonclassical 5-hydroxytryptamine receptor positively coupled with adenylate cyclase in the central nervous system. Mol Pharmacol. 1988 Dec;34(6):880–887. [PubMed] [Google Scholar]
  8. Glennon R. A., Naiman N. A., Pierson M. E., Titeler M., Lyon R. A., Weisberg E. NAN-190: an arylpiperazine analog that antagonizes the stimulus effects of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Eur J Pharmacol. 1988 Sep 23;154(3):339–341. doi: 10.1016/0014-2999(88)90212-9. [DOI] [PubMed] [Google Scholar]
  9. Göthert M. Presynaptic serotonin receptors in the central nervous system. Ann N Y Acad Sci. 1990;604:102–112. doi: 10.1111/j.1749-6632.1990.tb31986.x. [DOI] [PubMed] [Google Scholar]
  10. Haj-Dahmane S., Hamon M., Lanfumey L. K+ channel and 5-hydroxytryptamine1A autoreceptor interactions in the rat dorsal raphe nucleus: an in vitro electrophysiological study. Neuroscience. 1991;41(2-3):495–505. doi: 10.1016/0306-4522(91)90344-n. [DOI] [PubMed] [Google Scholar]
  11. Herrick-Davis K., Titeler M. Detection and characterization of the serotonin 5-HT 1D receptor in rat and human brain. J Neurochem. 1988 May;50(5):1624–1631. doi: 10.1111/j.1471-4159.1988.tb03052.x. [DOI] [PubMed] [Google Scholar]
  12. Heuring R. E., Peroutka S. J. Characterization of a novel 3H-5-hydroxytryptamine binding site subtype in bovine brain membranes. J Neurosci. 1987 Mar;7(3):894–903. doi: 10.1523/JNEUROSCI.07-03-00894.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hoyer D., Middlemiss D. N. Species differences in the pharmacology of terminal 5-HT autoreceptors in mammalian brain. Trends Pharmacol Sci. 1989 Apr;10(4):130–132. doi: 10.1016/0165-6147(89)90159-4. [DOI] [PubMed] [Google Scholar]
  14. Hoyer D., Pazos A., Probst A., Palacios J. M. Serotonin receptors in the human brain. I. Characterization and autoradiographic localization of 5-HT1A recognition sites. Apparent absence of 5-HT1B recognition sites. Brain Res. 1986 Jun 18;376(1):85–96. doi: 10.1016/0006-8993(86)90902-9. [DOI] [PubMed] [Google Scholar]
  15. Hoyer D., Pazos A., Probst A., Palacios J. M. Serotonin receptors in the human brain. II. Characterization and autoradiographic localization of 5-HT1C and 5-HT2 recognition sites. Brain Res. 1986 Jun 18;376(1):97–107. doi: 10.1016/0006-8993(86)90903-0. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Humphrey P. P., Feniuk W., Perren M. J., Connor H. E., Oxford A. W., Coates L. H., Butina D. GR43175, a selective agonist for the 5-HT1-like receptor in dog isolated saphenous vein. Br J Pharmacol. 1988 Aug;94(4):1123–1132. doi: 10.1111/j.1476-5381.1988.tb11630.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kenakin T. P. The classification of drugs and drug receptors in isolated tissues. Pharmacol Rev. 1984 Sep;36(3):165–222. [PubMed] [Google Scholar]
  19. Limberger N., Deicher R., Starke K. Species differences in presynaptic serotonin autoreceptors: mainly 5-HT1B but possibly in addition 5-HT1D in the rat, 5-HT1D in the rabbit and guinea-pig brain cortex. Naunyn Schmiedebergs Arch Pharmacol. 1991 Apr;343(4):353–364. doi: 10.1007/BF00179039. [DOI] [PubMed] [Google Scholar]
  20. Limberger N., Starke K., Singer E. A. Serotonin uptake blockers influence serotonin autoreceptors by increasing the biophase concentration of serotonin and not through a "molecular link". Naunyn Schmiedebergs Arch Pharmacol. 1990 Oct;342(4):363–370. doi: 10.1007/BF00169450. [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. Martin K. F., Marsden C. A. In vivo voltammetry in the suprachiasmatic nucleus of the rat: effects of RU24969, methiothepin and ketanserin. Eur J Pharmacol. 1986 Feb 11;121(1):135–139. doi: 10.1016/0014-2999(86)90403-6. [DOI] [PubMed] [Google Scholar]
  23. Mayer A., Limberger N., Starke K. Transmitter release patterns of noradrenergic, dopaminergic and cholinergic axons in rabbit brain slices during short pulse trains, and the operation of presynaptic autoreceptors. Naunyn Schmiedebergs Arch Pharmacol. 1988 Dec;338(6):632–643. doi: 10.1007/BF00165627. [DOI] [PubMed] [Google Scholar]
  24. Meltzer H. Y. Role of serotonin in depression. Ann N Y Acad Sci. 1990;600:486–500. doi: 10.1111/j.1749-6632.1990.tb16904.x. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Middlemiss D. N., Fozard J. R. 8-Hydroxy-2-(di-n-propylamino)-tetralin discriminates between subtypes of the 5-HT1 recognition site. Eur J Pharmacol. 1983 May 20;90(1):151–153. doi: 10.1016/0014-2999(83)90230-3. [DOI] [PubMed] [Google Scholar]
  27. Middlemiss D. N. The putative 5-HT1 receptor agonist, RU 24969, inhibits the efflux of 5-hydroxytryptamine from rat frontal cortex slices by stimulation of the 5-HT autoreceptor. J Pharm Pharmacol. 1985 Jun;37(6):434–437. doi: 10.1111/j.2042-7158.1985.tb03032.x. [DOI] [PubMed] [Google Scholar]
  28. Nyborg N. C. Action of noradrenaline on isolated proximal and distal coronary arteries of rat: selective release of endothelium-derived relaxing factor in proximal arteries. Br J Pharmacol. 1990 Jul;100(3):552–556. doi: 10.1111/j.1476-5381.1990.tb15845.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. O'Connor J. J., Kruk Z. L. Fast cyclic voltammetry can be used to measure stimulated endogenous 5-hydroxytryptamine release in untreated rat brain slices. J Neurosci Methods. 1991 Jun;38(1):25–33. doi: 10.1016/0165-0270(91)90150-x. [DOI] [PubMed] [Google Scholar]
  30. Palij P., Bull D. R., Sheehan M. J., Millar J., Stamford J., Kruk Z. L., Humphrey P. P. Presynaptic regulation of dopamine release in corpus striatum monitored in vitro in real time by fast cyclic voltammetry. Brain Res. 1990 Feb 12;509(1):172–174. doi: 10.1016/0006-8993(90)90329-a. [DOI] [PubMed] [Google Scholar]
  31. Pazos A., Hoyer D., Palacios J. M. The binding of serotonergic ligands to the porcine choroid plexus: characterization of a new type of serotonin recognition site. Eur J Pharmacol. 1984 Nov 27;106(3):539–546. doi: 10.1016/0014-2999(84)90057-8. [DOI] [PubMed] [Google Scholar]
  32. Pazos A., Palacios J. M. Quantitative autoradiographic mapping of serotonin receptors in the rat brain. I. Serotonin-1 receptors. Brain Res. 1985 Nov 4;346(2):205–230. doi: 10.1016/0006-8993(85)90856-x. [DOI] [PubMed] [Google Scholar]
  33. Peroutka S. J. 5-Hydroxytryptamine receptor subtypes. Annu Rev Neurosci. 1988;11:45–60. doi: 10.1146/annurev.ne.11.030188.000401. [DOI] [PubMed] [Google Scholar]
  34. Peroutka S. J. 5-Hydroxytryptamine receptor subtypes: molecular, biochemical and physiological characterization. Trends Neurosci. 1988 Nov;11(11):496–500. doi: 10.1016/0166-2236(88)90011-2. [DOI] [PubMed] [Google Scholar]
  35. Peroutka S. J., Snyder S. H. Multiple serotonin receptors: differential binding of [3H]5-hydroxytryptamine, [3H]lysergic acid diethylamide and [3H]spiroperidol. Mol Pharmacol. 1979 Nov;16(3):687–699. [PubMed] [Google Scholar]
  36. Richards C. D., Tegg W. J. A superfusion chamber suitable for maintaining mammalian brain tissue slices for electrical recording [proceedings]. Br J Pharmacol. 1977 Mar;59(3):526P–526P. [PMC free article] [PubMed] [Google Scholar]
  37. Saavedra J. M., Brownstein M., Palkovits M. Serotonin distribution in the limbic system of the rat. Brain Res. 1974 Oct 25;79(3):437–441. doi: 10.1016/0006-8993(74)90441-7. [DOI] [PubMed] [Google Scholar]
  38. Saavedra J. M., Palkovits M., Brownstein M. J., Axelrod J. Serotonin distribution in the nuclei of the rat hypothalamus and preoptic region. Brain Res. 1974 Aug 30;77(1):157–165. doi: 10.1016/0006-8993(74)90812-9. [DOI] [PubMed] [Google Scholar]
  39. Schoeffter P., Hoyer D. Interaction of arylpiperazines with 5-HT1A, 5-HT1B, 5-HT1C and 5-HT1D receptors: do discriminatory 5-HT1B receptor ligands exist? Naunyn Schmiedebergs Arch Pharmacol. 1989 Jun;339(6):675–683. doi: 10.1007/BF00168661. [DOI] [PubMed] [Google Scholar]
  40. Sharp T., Bramwell S. R., Grahame-Smith D. G. 5-HT1 agonists reduce 5-hydroxytryptamine release in rat hippocampus in vivo as determined by brain microdialysis. Br J Pharmacol. 1989 Feb;96(2):283–290. doi: 10.1111/j.1476-5381.1989.tb11815.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Sharp T., Bramwell S. R., Grahame-Smith D. G. Release of endogenous 5-hydroxytryptamine in rat ventral hippocampus evoked by electrical stimulation of the dorsal raphe nucleus as detected by microdialysis: sensitivity to tetrodotoxin, calcium and calcium antagonists. Neuroscience. 1990;39(3):629–637. doi: 10.1016/0306-4522(90)90247-2. [DOI] [PubMed] [Google Scholar]
  42. Shenker A., Maayani S., Weinstein H., Green J. P. Pharmacological characterization of two 5-hydroxytryptamine receptors coupled to adenylate cyclase in guinea pig hippocampal membranes. Mol Pharmacol. 1987 Apr;31(4):357–367. [PubMed] [Google Scholar]
  43. Sills M. A., Wolfe B. B., Frazer A. Determination of selective and nonselective compounds for the 5-HT 1A and 5-HT 1B receptor subtypes in rat frontal cortex. J Pharmacol Exp Ther. 1984 Dec;231(3):480–487. [PubMed] [Google Scholar]
  44. Singer E. A. Transmitter release from brain slices elicited by single pulses: a powerful method to study presynaptic mechanisms. Trends Pharmacol Sci. 1988 Aug;9(8):274–276. doi: 10.1016/0165-6147(88)90004-1. [DOI] [PubMed] [Google Scholar]
  45. Sprouse J. S., Aghajanian G. K. (-)-Propranolol blocks the inhibition of serotonergic dorsal raphe cell firing by 5-HT1A selective agonists. Eur J Pharmacol. 1986 Sep 9;128(3):295–298. doi: 10.1016/0014-2999(86)90782-x. [DOI] [PubMed] [Google Scholar]
  46. Sprouse J. S., Aghajanian G. K. Electrophysiological responses of serotoninergic dorsal raphe neurons to 5-HT1A and 5-HT1B agonists. Synapse. 1987;1(1):3–9. doi: 10.1002/syn.890010103. [DOI] [PubMed] [Google Scholar]
  47. Starke K., Göthert M., Kilbinger H. Modulation of neurotransmitter release by presynaptic autoreceptors. Physiol Rev. 1989 Jul;69(3):864–989. doi: 10.1152/physrev.1989.69.3.864. [DOI] [PubMed] [Google Scholar]
  48. Valenta B., Drobny H., Singer E. A. Presynaptic autoinhibition of central noradrenaline release in vitro: operational characteristics and effects of drugs acting at alpha-2 adrenoceptors in the presence of uptake inhibition. J Pharmacol Exp Ther. 1988 Jun;245(3):944–949. [PubMed] [Google Scholar]
  49. VanderMaelen C. P., Matheson G. K., Wilderman R. C., Patterson L. A. Inhibition of serotonergic dorsal raphe neurons by systemic and iontophoretic administration of buspirone, a non-benzodiazepine anxiolytic drug. Eur J Pharmacol. 1986 Sep 23;129(1-2):123–130. doi: 10.1016/0014-2999(86)90343-2. [DOI] [PubMed] [Google Scholar]
  50. Waeber C., Schoeffter P., Palacios J. M., Hoyer D. Molecular pharmacology of 5-HT1D recognition sites: radioligand binding studies in human, pig and calf brain membranes. Naunyn Schmiedebergs Arch Pharmacol. 1988 Jun;337(6):595–601. doi: 10.1007/BF00175783. [DOI] [PubMed] [Google Scholar]
  51. de Montigny C., Blier P., Chaput Y. Electrophysiologically-identified serotonin receptors in the rat CNS. Effect of antidepressant treatment. Neuropharmacology. 1984 Dec;23(12B):1511–1520. doi: 10.1016/0028-3908(84)90095-9. [DOI] [PubMed] [Google Scholar]

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