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. 1996 Nov;119(5):845–850. doi: 10.1111/j.1476-5381.1996.tb15749.x

Possible in vivo 5-HT reuptake blocking properties of 8-OH-DPAT assessed by measuring hippocampal extracellular 5-HT using microdialysis in rats.

M B Assié 1, W Koek 1
PMCID: PMC1915946  PMID: 8922730

Abstract

1. The 5-hydroxytryptamine (5-HT)1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), has been shown to label 5-HT reuptake sites. 2. To study the functional consequences of this property, the effects of 8-OH-DPAT were compared with those of the 5-HT reuptake inhibitors, paroxetine and clomipramine, and of the 5-HT1A receptor agonist flesinoxan, in vitro on 5-HT reuptake, and in vivo on the extracellular concentration of 5-HT by use of microdialysis, in rat hippocampus. Because 5-HT reuptake inhibitors reportedly attenuate the ability of (+)-fenfluramine to increase the extracellular concentration of 5-HT, the possible reversal of these effects of 8-OH-DPAT and by paroxetine were examined. 3. 8-OH-DPAT, paroxetine and clomipramine inhibited [3H]-5-HT reuptake in rat hippocampal synaptosomes (pIC50: 6.00, 8.41 and 7.00, respectively). In contrast, flesinoxan did not alter 5-HT reuptake (pIC50 < 5). 4. 8-OH-DPAT (10 and 100 microM), paroxetine (0.1 microM) and clomipramine (1 microM), administered through the dialysis probe, significantly increased the hippocampal extracellular concentration of 5-HT. In contrast, flesinoxan (100 microM) did not alter extracellular 5-HT. Moreover, the effects of 100 microM 8-OH-DPAT were not blocked by the 5-HT1A receptor antagonist, WAY-100635 (0.16 mg kg-1, s.c.). 5. The increase in extracellular 5-HT induced by 10 mg kg-1, i.p., (+)-fenfluramine was prevented not only by 0.1 microM paroxetine, but also by 100 microM 8-OH-DPAT. In addition, systemic administration of 10 mg kg-1, but not 2.5 mg kg-1, i.p. 8-OH-DPAT attenuated the increase in extracellular 5-HT induced by 2.5 mg kg-1, i.p., (+)-fenfluramine. 6. These findings suggest that the increase in extracellular 5-HT produced by local administration of 8-OH-DPAT does not involve its 5-HT1A receptor agonist properties, but may result, at least in part, from its 5-HT reuptake blocking properties.

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Selected References

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  1. Adell A., Carceller A., Artigas F. In vivo brain dialysis study of the somatodendritic release of serotonin in the Raphe nuclei of the rat: effects of 8-hydroxy-2-(di-n-propylamino)tetralin. J Neurochem. 1993 May;60(5):1673–1681. doi: 10.1111/j.1471-4159.1993.tb13390.x. [DOI] [PubMed] [Google Scholar]
  2. Alexander B. S., Wood M. D. [3H]8-OH-DPAT labels the 5-hydroxytryptamine uptake recognition site and the 5-HT1A binding site in the rat striatum. J Pharm Pharmacol. 1988 Dec;40(12):888–891. doi: 10.1111/j.2042-7158.1988.tb06296.x. [DOI] [PubMed] [Google Scholar]
  3. Assie M. B., Koek W. (-)-pindolol and (+/-)-tertatolol affect rat hippocampal 5-HT levels through mechanisms involving not only 5-HT1A, but also 5-HT1B receptors. Neuropharmacology. 1996 Feb;35(2):213–222. doi: 10.1016/0028-3908(95)00169-7. [DOI] [PubMed] [Google Scholar]
  4. Assié M. B., Koek W. Effects of 5-HT1A receptor antagonists on hippocampal 5-hydroxytryptamine levels: (S)-WAY100135, but not WAY100635, has partial agonist properties. Eur J Pharmacol. 1996 May 23;304(1-3):15–21. doi: 10.1016/0014-2999(96)00086-6. [DOI] [PubMed] [Google Scholar]
  5. Auerbach S. B., Lundberg J. F., Hjorth S. Differential inhibition of serotonin release by 5-HT and NA reuptake blockers after systemic administration. Neuropharmacology. 1995 Jan;34(1):89–96. doi: 10.1016/0028-3908(94)00137-h. [DOI] [PubMed] [Google Scholar]
  6. Benveniste H. Brain microdialysis. J Neurochem. 1989 Jun;52(6):1667–1679. doi: 10.1111/j.1471-4159.1989.tb07243.x. [DOI] [PubMed] [Google Scholar]
  7. Bosker F. J., de Winter T. Y., Klompmakers A. A., Westenberg H. G. Flesinoxan dose-dependently reduces extracellular 5-hydroxytryptamine (5-HT) in rat median raphe and dorsal hippocampus through activation of 5-HT1A receptors. J Neurochem. 1996 Jun;66(6):2546–2555. doi: 10.1046/j.1471-4159.1996.66062546.x. [DOI] [PubMed] [Google Scholar]
  8. Bosker F., Klompmakers A., Westenberg H. Extracellular 5-hydroxytryptamine in median raphe nucleus of the conscious rat is decreased by nanomolar concentrations of 8-hydroxy-2-(di-n-propylamino) tetralin and is sensitive to tetrodotoxin. J Neurochem. 1994 Dec;63(6):2165–2171. doi: 10.1046/j.1471-4159.1994.63062165.x. [DOI] [PubMed] [Google Scholar]
  9. Cheng C. H., Costall B., Naylor R. J., Rudd J. A. The effect of 5-HT receptor ligands on the uptake of [3H]5-hydroxytryptamine into rat cortical synaptosomes. Eur J Pharmacol. 1993 Aug 3;239(1-3):211–214. doi: 10.1016/0014-2999(93)90996-u. [DOI] [PubMed] [Google Scholar]
  10. Forster E. A., Cliffe I. A., Bill D. J., Dover G. M., Jones D., Reilly Y., Fletcher A. A pharmacological profile of the selective silent 5-HT1A receptor antagonist, WAY-100635. Eur J Pharmacol. 1995 Jul 25;281(1):81–88. doi: 10.1016/0014-2999(95)00234-c. [DOI] [PubMed] [Google Scholar]
  11. Fuller R. W. Uptake inhibitors increase extracellular serotonin concentration measured by brain microdialysis. Life Sci. 1994;55(3):163–167. doi: 10.1016/0024-3205(94)00876-0. [DOI] [PubMed] [Google Scholar]
  12. Hamon M., Bourgoin S., Gozlan H., Hall M. D., Goetz C., Artaud F., Horn A. S. Biochemical evidence for the 5-HT agonist properties of PAT (8-hydroxy-2-(di-n-propylamino)tetralin) in the rat brain. Eur J Pharmacol. 1984 May 4;100(3-4):263–276. doi: 10.1016/0014-2999(84)90002-5. [DOI] [PubMed] [Google Scholar]
  13. Ieni J. R., Meyerson L. R. The 5-HT1A receptor probe [3H]8-OH-DPAT labels the 5-HT transporter in human platelets. Life Sci. 1988;42(3):311–320. doi: 10.1016/0024-3205(88)90640-6. [DOI] [PubMed] [Google Scholar]
  14. Kreiss D. S., Lucki I. Differential regulation of serotonin (5-HT) release in the striatum and hippocampus by 5-HT1A autoreceptors of the dorsal and median raphe nuclei. J Pharmacol Exp Ther. 1994 Jun;269(3):1268–1279. [PubMed] [Google Scholar]
  15. Kreiss D. S., Wieland S., Lucki I. The presence of a serotonin uptake inhibitor alters pharmacological manipulations of serotonin release. Neuroscience. 1993 Jan;52(2):295–301. doi: 10.1016/0306-4522(93)90157-b. [DOI] [PubMed] [Google Scholar]
  16. Laferrere B., Wurtman R. J. Effect of D-fenfluramine on serotonin release in brains of anaesthetized rats. Brain Res. 1989 Dec 18;504(2):258–263. doi: 10.1016/0006-8993(89)91365-6. [DOI] [PubMed] [Google Scholar]
  17. Nakahata N., Ishimoto H., Mizuno K., Ohizumi Y., Nakanishi H. Dual effects of mastoparan on intracellular free Ca2+ concentrations in human astrocytoma cells. Br J Pharmacol. 1994 May;112(1):299–303. doi: 10.1111/j.1476-5381.1994.tb13068.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Sabol K. E., Richards J. B., Seiden L. S. Fluoxetine attenuates the DL-fenfluramine-induced increase in extracellular serotonin as measured by in vivo dialysis. Brain Res. 1992 Jul 10;585(1-2):421–424. doi: 10.1016/0006-8993(92)91249-e. [DOI] [PubMed] [Google Scholar]
  19. Sarkissian C. F., Wurtman R. J., Morse A. N., Gleason R. Effects of fluoxetine or D-fenfluramine on serotonin release from, and levels in, rat frontal cortex. Brain Res. 1990 Oct 8;529(1-2):294–301. doi: 10.1016/0006-8993(90)90840-8. [DOI] [PubMed] [Google Scholar]
  20. Schoemaker H., Langer S. Z. [3H]8-OH-DPAT labels the serotonin transporter in the rat striatum. Eur J Pharmacol. 1986 May 27;124(3):371–373. doi: 10.1016/0014-2999(86)90243-8. [DOI] [PubMed] [Google Scholar]
  21. Series H. G., Cowen P. J., Sharp T. p-Chloroamphetamine (PCA), 3,4-methylenedioxy-methamphetamine (MDMA) and d-fenfluramine pretreatment attenuates d-fenfluramine-evoked release of 5-HT in vivo. Psychopharmacology (Berl) 1994 Dec;116(4):508–514. doi: 10.1007/BF02247485. [DOI] [PubMed] [Google Scholar]
  22. Sharp T., Bramwell S. R., Clark D., Grahame-Smith D. G. In vivo measurement of extracellular 5-hydroxytryptamine in hippocampus of the anaesthetized rat using microdialysis: changes in relation to 5-hydroxytryptaminergic neuronal activity. J Neurochem. 1989 Jul;53(1):234–240. doi: 10.1111/j.1471-4159.1989.tb07319.x. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Sharp T., Hjorth S. Application of brain microdialysis to study the pharmacology of the 5-HT1A autoreceptor. J Neurosci Methods. 1990 Sep;34(1-3):83–90. doi: 10.1016/0165-0270(90)90045-h. [DOI] [PubMed] [Google Scholar]
  25. Sprouse J. S., McCarty D. R., Dudley M. W. Apparent regional differences in 5-HT1A binding may reflect [3H]8-OH-DPAT labeling of serotonin uptake sites. Brain Res. 1993 Jul 16;617(1):159–162. doi: 10.1016/0006-8993(93)90629-2. [DOI] [PubMed] [Google Scholar]
  26. Thomas D. R., Nelson D. R., Johnson A. M. Biochemical effects of the antidepressant paroxetine, a specific 5-hydroxytryptamine uptake inhibitor. Psychopharmacology (Berl) 1987;93(2):193–200. doi: 10.1007/BF00179933. [DOI] [PubMed] [Google Scholar]

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