Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1995 Jun;115(4):703–711. doi: 10.1111/j.1476-5381.1995.tb14990.x

Increase of noradrenaline release in the hypothalamus of freely moving rat by postsynaptic 5-hydroxytryptamine1A receptor activation.

M Suzuki 1, T Matsuda 1, S Asano 1, P Somboonthum 1, K Takuma 1, A Baba 1
PMCID: PMC1908488  PMID: 7582494

Abstract

1. 5-Hydroxytryptamine (5-HT) plays a role in the regulation of noradrenergic neurones in the brain, but the precise mechanism of regulation of noradrenaline (NA) release by 5-HT1A receptors has not been defined. The present study describes the effect of a highly potent and selective 5-HT1A receptor agonist, 5-(3-[[(2S)-1,4-benzodioxan-2-ylmethyl)]amino]propoxy)-1,3-b enzodioxole HC1 (MKC-242), on NA release in the hypothalamus using microdialysis in the freely moving rat. 2. Subcutaneous injection of MKC-242 (0.5 mg kg-1) increased extracellular levels of NA and its metabolite, 3-methoxy-4-hydroxyphenylglycol, in the hypothalamus and hippocampus. 3. The 5-HT1A receptor agonists, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) (0.2 mg kg-1) and buspirone (3 mg kg-1) mimicked the effect of MKC-242 in increasing NA release in the hypothalamus. 4. The effects of MKC-242 and 8-OH-DPAT in the hypothalamus were antagonized by pretreatment with WAY100135 (10 mg kg-1), a silent 5-HT1A receptor antagonist. 5. Local administration of 8-OH-DPAT (10-100 microM), citalopram (1 microM), a 5-HT reuptake inhibitor, and MDL72222 (10 microM), a 5-HT3 receptor antagonist, into the hypothalamus, had no effect on NA release. 6. Intracerebroventricular injection with 5,7-dihydroxytryptamine caused a marked reduction in brain 5-HT content, but the treatment affected neither basal NA levels nor the MKC-242-induced increase in NA release. 7. The effect of MKC-242 in increasing NA release was not attenuated by repeated treatment with the drug (0.5 mg kg-1, once a day for 2 weeks).(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
703

Selected References

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

  1. Beer M., Kennett G. A., Curzon G. A single dose of 8-OH-DPAT reduces raphe binding of [3H]8-OH-DPAT and increases the effect of raphe stimulation on 5-HT metabolism. Eur J Pharmacol. 1990 Mar 20;178(2):179–187. doi: 10.1016/0014-2999(90)90473-j. [DOI] [PubMed] [Google Scholar]
  2. Bianchi G., Caccia S., Della Vedova F., Garattini S. The alpha 2-adrenoceptor antagonist activity of ipsapirone and gepirone is mediated by their common metabolite 1-(2-pyrimidinyl)-piperazine (PmP). Eur J Pharmacol. 1988 Jul 14;151(3):365–371. doi: 10.1016/0014-2999(88)90532-8. [DOI] [PubMed] [Google Scholar]
  3. Blandina P., Goldfarb J., Walcott J., Green J. P. Serotonergic modulation of the release of endogenous norepinephrine from rat hypothalamic slices. J Pharmacol Exp Ther. 1991 Jan;256(1):341–347. [PubMed] [Google Scholar]
  4. Blier P., de Montigny C. Modification of 5-HT neuron properties by sustained administration of the 5-HT1A agonist gepirone: electrophysiological studies in the rat brain. Synapse. 1987;1(5):470–480. doi: 10.1002/syn.890010511. [DOI] [PubMed] [Google Scholar]
  5. Broderick P. A., Piercey M. F. 5-HT1A agonists uncouple noradrenergic somatodendritic impulse flow and terminal release. Brain Res Bull. 1991 Nov;27(5):693–696. doi: 10.1016/0361-9230(91)90047-n. [DOI] [PubMed] [Google Scholar]
  6. Butler P. D., Pranzatelli M. R., Barkai A. I. Regional central serotonin-2 receptor binding and phosphoinositide turnover in rats with 5,7-dihydroxytryptamine lesions. Brain Res Bull. 1990 Jan;24(1):125–129. doi: 10.1016/0361-9230(90)90296-c. [DOI] [PubMed] [Google Scholar]
  7. Clement H. W., Gemsa D., Wesemann W. Serotonin-norepinephrine interactions: a voltammetric study on the effect of serotonin receptor stimulation followed in the N. raphe dorsalis and the Locus coeruleus of the rat. J Neural Transm Gen Sect. 1992;88(1):11–23. doi: 10.1007/BF01245033. [DOI] [PubMed] [Google Scholar]
  8. Crespi F., Buda M., McRae-Degueurce A., Pujol J. F. Alteration of tyrosine hydroxylase activity in the locus coeruleus after administration of p-chlorophenylalanine. Brain Res. 1980 Jun 9;191(2):501–509. doi: 10.1016/0006-8993(80)91298-6. [DOI] [PubMed] [Google Scholar]
  9. Crist J., Surprenant A. Evidence that 8-hydroxy-2-(n-dipropylamino)tetralin (8-OH-DPAT) is a selective alpha 2-adrenoceptor antagonist on guinea-pig submucous neurones. Br J Pharmacol. 1987 Oct;92(2):341–347. doi: 10.1111/j.1476-5381.1987.tb11329.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Done C. J., Sharp T. Biochemical evidence for the regulation of central noradrenergic activity by 5-HT1A and 5-HT2 receptors: microdialysis studies in the awake and anaesthetized rat. Neuropharmacology. 1994 Mar-Apr;33(3-4):411–421. doi: 10.1016/0028-3908(94)90071-x. [DOI] [PubMed] [Google Scholar]
  11. Done C. J., Sharp T. Evidence that 5-HT2 receptor activation decreases noradrenaline release in rat hippocampus in vivo. Br J Pharmacol. 1992 Sep;107(1):240–245. doi: 10.1111/j.1476-5381.1992.tb14493.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Feuerstein T. J., Hertting G. Serotonin (5-HT) enhances hippocampal noradrenaline (NA) release: evidence for facilitatory 5-HT receptors within the CNS. Naunyn Schmiedebergs Arch Pharmacol. 1986 Jul;333(3):191–197. doi: 10.1007/BF00512929. [DOI] [PubMed] [Google Scholar]
  13. Fuller R. W., Perry K. W. Effects of buspirone and its metabolite, 1-(2-pyrimidinyl)piperazine, on brain monoamines and their metabolites in rats. J Pharmacol Exp Ther. 1989 Jan;248(1):50–56. [PubMed] [Google Scholar]
  14. Gartside S. E., Cowen P. J., Hjorth S. Effects of MDL 73005EF on central pre- and postsynaptic 5-HT1A receptor function in the rat in vivo. Eur J Pharmacol. 1990 Dec 4;191(3):391–400. doi: 10.1016/0014-2999(90)94173-u. [DOI] [PubMed] [Google Scholar]
  15. Gobbi M., Frittoli E., Mennini T. Antagonist properties of 1-(2-pyrimidinyl)piperazine at presynaptic alpha 2-adrenoceptors in the rat brain. Eur J Pharmacol. 1990 May 3;180(1):183–186. doi: 10.1016/0014-2999(90)90608-9. [DOI] [PubMed] [Google Scholar]
  16. Godbout R., Chaput Y., Blier P., de Montigny C. Tandospirone and its metabolite, 1-(2-pyrimidinyl)-piperazine--I. Effects of acute and long-term administration of tandospirone on serotonin neurotransmission. Neuropharmacology. 1991 Jul;30(7):679–690. doi: 10.1016/0028-3908(91)90175-b. [DOI] [PubMed] [Google Scholar]
  17. Gorea E., Adrien J. Serotonergic regulation of noradrenergic coerulean neurons: electrophysiological evidence for the involvement of 5-HT2 receptors. Eur J Pharmacol. 1988 Sep 23;154(3):285–291. doi: 10.1016/0014-2999(88)90203-8. [DOI] [PubMed] [Google Scholar]
  18. Gorea E., Davenne D., Lanfumey L., Chastanet M., Adrien J. Regulation of noradrenergic coerulean neuronal firing mediated by 5-HT2 receptors: involvement of the prepositus hypoglossal nucleus. Neuropharmacology. 1991 Dec;30(12A):1309–1318. doi: 10.1016/0028-3908(91)90028-a. [DOI] [PubMed] [Google Scholar]
  19. Greuel J. M., Glaser T. The putative 5-HT1A receptor antagonists NAN-190 and BMY 7378 are partial agonists in the rat dorsal raphe nucleus in vitro. Eur J Pharmacol. 1992 Feb 11;211(2):211–219. doi: 10.1016/0014-2999(92)90531-8. [DOI] [PubMed] [Google Scholar]
  20. Heal D. J., Hurst E. M., Prow M. R., Buckett W. R. An investigation of the role of 5-hydroxytryptamine in the attenuation of presynaptic alpha 2-adrenoceptor-mediated responses by antidepressant treatments. Psychopharmacology (Berl) 1990;101(1):100–106. doi: 10.1007/BF02253725. [DOI] [PubMed] [Google Scholar]
  21. Hjorth S., Auerbach S. B. Lack of 5-HT1A autoreceptor desensitization following chronic citalopram treatment, as determined by in vivo microdialysis. Neuropharmacology. 1994 Mar-Apr;33(3-4):331–334. doi: 10.1016/0028-3908(94)90062-0. [DOI] [PubMed] [Google Scholar]
  22. Hjorth S., Sharp T. Mixed agonist/antagonist properties of NAN-190 at 5-HT1A receptors: behavioural and in vivo brain microdialysis studies. Life Sci. 1990;46(13):955–963. doi: 10.1016/0024-3205(90)90097-b. [DOI] [PubMed] [Google Scholar]
  23. Kreiss D. S., Lucki I. Desensitization of 5-HT1A autoreceptors by chronic administration of 8-OH-DPAT. Neuropharmacology. 1992 Oct;31(10):1073–1076. doi: 10.1016/0028-3908(92)90110-b. [DOI] [PubMed] [Google Scholar]
  24. Larsson L. G., Rényi L., Ross S. B., Svensson B., Angeby-Möller K. Different effects on the responses of functional pre- and postsynaptic 5-HT1A receptors by repeated treatment of rats with the 5-HT1A receptor agonist 8-OH-DPAT. Neuropharmacology. 1990 Feb;29(2):85–91. doi: 10.1016/0028-3908(90)90047-u. [DOI] [PubMed] [Google Scholar]
  25. Matsuda T., Seong Y. H., Aono H., Kanda T., Baba A., Saito K., Tobe A., Iwata H. Agonist activity of a novel compound, 1-[3-(3,4-methylenedioxyphenoxy)propyl]-4-phenyl piperazine (BP-554), at central 5-HT1A receptors. Eur J Pharmacol. 1989 Oct 24;170(1-2):75–82. doi: 10.1016/0014-2999(89)90136-2. [DOI] [PubMed] [Google Scholar]
  26. Nakano Y., Matsuda T., Takuma K., Yoshikawa T., Baba A. Sex difference for tolerance of 5-HT1A receptor-mediated temperature and corticosterone responses in mice. Eur J Pharmacol. 1992 Aug 25;219(2):339–341. doi: 10.1016/0014-2999(92)90317-w. [DOI] [PubMed] [Google Scholar]
  27. Nash J. F., Jr, Meltzer H. Y., Gudelsky G. A. Selective cross-tolerance to 5-HT1A and 5-HT2 receptor-mediated temperature and corticosterone responses. Pharmacol Biochem Behav. 1989 Aug;33(4):781–785. doi: 10.1016/0091-3057(89)90470-x. [DOI] [PubMed] [Google Scholar]
  28. Pickel V. M., Joh T. H., Reis D. J. A serotonergic innervation of noradrenergic neurons in nucleus locus coeruleus: demonstration by immunocytochemical localization of the transmitter specific enzymes tyrosine and tryptophan hydroxylase. Brain Res. 1977 Aug 12;131(2):197–214. doi: 10.1016/0006-8993(77)90515-7. [DOI] [PubMed] [Google Scholar]
  29. Qadri F., Badoer E., Stadler T., Unger T. Angiotensin II-induced noradrenaline release from anterior hypothalamus in conscious rats: a brain microdialysis study. Brain Res. 1991 Nov 1;563(1-2):137–141. doi: 10.1016/0006-8993(91)91526-7. [DOI] [PubMed] [Google Scholar]
  30. Rasmussen K., Aghajanian G. K. Effect of hallucinogens on spontaneous and sensory-evoked locus coeruleus unit activity in the rat: reversal by selective 5-HT2 antagonists. Brain Res. 1986 Oct 22;385(2):395–400. doi: 10.1016/0006-8993(86)91090-5. [DOI] [PubMed] [Google Scholar]
  31. Reader T. A., Brière R., Grondin L., Ferron A. Effects of p-chlorophenylalanine on cortical monoamines and on the activity of noradrenergic neurons. Neurochem Res. 1986 Jul;11(7):1025–1035. doi: 10.1007/BF00965591. [DOI] [PubMed] [Google Scholar]
  32. Renaud B., Buda M., Lewis B. D., Pujol J. F. Effects of 5,6-dihydroxytryptamine on tyrosine-hydroxylase activity in central catecholaminergic neurons of the rat. Biochem Pharmacol. 1975 Sep 15;24(18):1739–1742. doi: 10.1016/0006-2952(75)90018-0. [DOI] [PubMed] [Google Scholar]
  33. Routledge C., Gurling J., Wright I. K., Dourish C. T. Neurochemical profile of the selective and silent 5-HT1A receptor antagonist WAY100135: an in vivo microdialysis study. Eur J Pharmacol. 1993 Aug 3;239(1-3):195–202. doi: 10.1016/0014-2999(93)90994-s. [DOI] [PubMed] [Google Scholar]
  34. Sharp T., McQuade R., Bramwell S., Hjorth S. Effect of acute and repeated administration of 5-HT1A receptor agonists on 5-HT release in rat brain in vivo. Naunyn Schmiedebergs Arch Pharmacol. 1993 Oct;348(4):339–346. doi: 10.1007/BF00171331. [DOI] [PubMed] [Google Scholar]
  35. Sprouse J. S. Inhibition of dorsal raphe cell firing by MDL 73005EF, a novel 5-HT1A receptor ligand. Eur J Pharmacol. 1991 Aug 29;201(2-3):163–169. doi: 10.1016/0014-2999(91)90340-v. [DOI] [PubMed] [Google Scholar]
  36. Steinbusch H. W. Distribution of serotonin-immunoreactivity in the central nervous system of the rat-cell bodies and terminals. Neuroscience. 1981;6(4):557–618. doi: 10.1016/0306-4522(81)90146-9. [DOI] [PubMed] [Google Scholar]
  37. Söderpalm B., Lundin B., Hjorth S. Sustained 5-hydroxytryptamine release-inhibitory and anxiolytic-like action of the partial 5-HT1A receptor agonist, buspirone, after prolonged chronic administration. Eur J Pharmacol. 1993 Aug 3;239(1-3):69–73. doi: 10.1016/0014-2999(93)90977-p. [DOI] [PubMed] [Google Scholar]
  38. Tian Y., Eaton M. J., Goudreau J. L., Lookingland K. J., Moore K. E. Neurochemical evidence that 5-hydroxytryptaminergic neurons tonically inhibit noradrenergic neurons terminating in the hypothalamus. Brain Res. 1993 Apr 2;607(1-2):215–221. doi: 10.1016/0006-8993(93)91509-q. [DOI] [PubMed] [Google Scholar]

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

RESOURCES