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. 1992 Sep;107(1):240–245. doi: 10.1111/j.1476-5381.1992.tb14493.x

Evidence that 5-HT2 receptor activation decreases noradrenaline release in rat hippocampus in vivo.

C J Done 1, T Sharp 1
PMCID: PMC1907589  PMID: 1422575

Abstract

1. Recent electrophysiological studies have shown that 5-HT2/5-HT1C receptor agonists inhibit the electrical activity of noradrenergic neurones in the rat locus coeruleus. Here we examine the effect of various agonists and antagonists of 5-HT2/5-HT1C receptors on noradrenaline release in hippocampus of anaesthetized rats using microdialysis. 2. Subcutaneous administration of the 5-HT2/5-HT1C receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI: 0.2 and 0.5 mg kg-1), caused a marked decrease (50% of pre-drug levels 60 min after injection) of noradrenaline in hippocampal dialysates which was long-lasting (greater than 120 min). Noradrenaline output also decreased in response to administration of the structural analogue of DOI, 1-(2,5-dimethoxy-4-bromophenyl)-2-aminopropane (DOB: 1 mg kg-1, s.c.). 3. The effect of DOI on noradrenaline output was prevented by pretreatment with the 5-HT2/5-HT1C receptor antagonist, ritanserin (0.4 mg kg-1, s.c.). Spiperone (0.2 and 1 mg kg-1, s.c.), a 5-HT2/dopamine D2 receptor antagonist which has low affinity for 5-HT1C receptors, also antagonized the effect of DOI (0.5 mg kg-1, s.c.). Sulpiride (50 mg kg-1, s.c.), a dopamine D2 receptor antagonist did not alter the response to DOI (0.5 mg kg-1, s.c.). 4. Both the non-selective 5-HT receptor agonist, quipazine (1 mg kg-1, s.c.), and the 5-HT-releasing agent, p-chloroamphetamine (2 mg kg-1, s.c.), decreased noradrenaline release in hippocampus and these effects were antagonized by pretreatment with ritanserin (0.4 mg kg-1, s.c.).(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Abercrombie E. D., Keller R. W., Jr, Zigmond M. J. Characterization of hippocampal norepinephrine release as measured by microdialysis perfusion: pharmacological and behavioral studies. Neuroscience. 1988 Dec;27(3):897–904. doi: 10.1016/0306-4522(88)90192-3. [DOI] [PubMed] [Google Scholar]
  2. Appel N. M., Mitchell W. M., Garlick R. K., Glennon R. A., Teitler M., De Souza E. B. Autoradiographic characterization of (+-)-1-(2,5-dimethoxy-4-[125I] iodophenyl)-2-aminopropane ([125I]DOI) binding to 5-HT2 and 5-HT1c receptors in rat brain. J Pharmacol Exp Ther. 1990 Nov;255(2):843–857. [PubMed] [Google Scholar]
  3. 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]
  4. 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]
  5. De Souza E. B., Kuyatt B. L. Autoradiographic localization of 3H-paroxetine-labeled serotonin uptake sites in rat brain. Synapse. 1987;1(5):488–496. doi: 10.1002/syn.890010513. [DOI] [PubMed] [Google Scholar]
  6. Done C., Silverstone P., Sharp T. Effect of naloxone-precipitated morphine withdrawal on noradrenaline release in rat hippocampus in vivo. Eur J Pharmacol. 1992 May 14;215(2-3):333–336. doi: 10.1016/0014-2999(92)90052-6. [DOI] [PubMed] [Google Scholar]
  7. Ferron A. Modified coeruleo-cortical noradrenergic neurotransmission after serotonin depletion by PCPA: electrophysiological studies in the rat. Synapse. 1988;2(5):532–536. doi: 10.1002/syn.890020509. [DOI] [PubMed] [Google Scholar]
  8. Foote S. L., Bloom F. E., Aston-Jones G. Nucleus locus ceruleus: new evidence of anatomical and physiological specificity. Physiol Rev. 1983 Jul;63(3):844–914. doi: 10.1152/physrev.1983.63.3.844. [DOI] [PubMed] [Google Scholar]
  9. Glennon R. A., McKenney J. D., Lyon R. A., Titeler M. 5-HT1 and 5-HT2 binding characteristics of 1-(2,5-dimethoxy-4-bromophenyl)-2-aminopropane analogues. J Med Chem. 1986 Feb;29(2):194–199. doi: 10.1021/jm00152a005. [DOI] [PubMed] [Google Scholar]
  10. Glennon R. A., Young R., Rosecrans J. A. Antagonism of the effects of the hallucinogen DOM and the purported 5-HT agonist quipazine by 5-HT2 antagonists. Eur J Pharmacol. 1983 Jul 22;91(2-3):189–196. doi: 10.1016/0014-2999(83)90464-8. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. 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]
  13. Hoyer D. Functional correlates of serotonin 5-HT1 recognition sites. J Recept Res. 1988;8(1-4):59–81. doi: 10.3109/10799898809048978. [DOI] [PubMed] [Google Scholar]
  14. Kalén P., Kokaia M., Lindvall O., Björklund A. Basic characteristics of noradrenaline release in the hippocampus of intact and 6-hydroxydopamine-lesioned rats as studied by in vivo microdialysis. Brain Res. 1988 Dec 6;474(2):374–379. doi: 10.1016/0006-8993(88)90454-4. [DOI] [PubMed] [Google Scholar]
  15. Leger L., Descarries L. Serotonin nerve terminals in the locus coeruleus of adult rat: a radioautographic study. Brain Res. 1978 Apr 21;145(1):1–13. doi: 10.1016/0006-8993(78)90791-6. [DOI] [PubMed] [Google Scholar]
  16. Peroutka S. J., Lebovitz R. M., Snyder S. H. Two distinct central serotonin receptors with different physiological functions. Science. 1981 May 15;212(4496):827–829. doi: 10.1126/science.7221567. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. 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]
  19. 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]
  20. Rasmussen K., Glennon R. A., Aghajanian G. K. Phenethylamine hallucinogens in the locus coeruleus: potency of action correlates with rank order of 5-HT2 binding affinity. Eur J Pharmacol. 1986 Dec 2;132(1):79–82. doi: 10.1016/0014-2999(86)90014-2. [DOI] [PubMed] [Google Scholar]
  21. Savaki H., Malgouris C., Bénavidès J., Laplace C., Uzan A., Guérémy C., Le Fur G. Quantitative autoradiography of [3H]indalpine binding sites in the rat brain: II. Regional distribution. J Neurochem. 1985 Aug;45(2):521–526. doi: 10.1111/j.1471-4159.1985.tb04019.x. [DOI] [PubMed] [Google Scholar]
  22. Sharp T., Zetterström T., Christmanson L., Ungerstedt U. p-Chloroamphetamine releases both serotonin and dopamine into rat brain dialysates in vivo. Neurosci Lett. 1986 Dec 23;72(3):320–324. doi: 10.1016/0304-3940(86)90534-3. [DOI] [PubMed] [Google Scholar]
  23. Stefanini E., Marchisio A. M., Devoto P., Vernaleone F., Collu R., Spano P. F. Sodium-dependent interaction of benzamides with dopamine receptors. Brain Res. 1980 Sep 29;198(1):229–233. doi: 10.1016/0006-8993(80)90360-1. [DOI] [PubMed] [Google Scholar]
  24. Vetulani J., Bednarczyk B., Reichenberg K., Rokosz A. Head twitches induced by LSD and quipazine: similarities and differences. Neuropharmacology. 1980 Feb;19(2):155–158. doi: 10.1016/0028-3908(80)90131-8. [DOI] [PubMed] [Google Scholar]
  25. Wing L. L., Tapson G. S., Geyer M. A. 5HT-2 mediation of acute behavioral effects of hallucinogens in rats. Psychopharmacology (Berl) 1990;100(3):417–425. doi: 10.1007/BF02244617. [DOI] [PubMed] [Google Scholar]

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