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. 1996 Mar;21(2):114–122.

[3H]8-OH-DPAT binding and serotonin content in rat cerebral cortex after acute fluoxetine, desipramine, or pargyline.

M Carli 1, S Afkhami-Dastjerdian 1, T A Reader 1
PMCID: PMC1188750  PMID: 8820177

Abstract

Cortical serotonin1A (5-HT1A) receptors in the rat were studied following acute (24 hours) intraperitoneal administrations of the 5-HT uptake inhibitor fluoxetine (10 mg/kg), the antidepressant desipramine (20 mg/kg), or the monoamine oxidase (MAO) inhibitor pargyline (75 mg/kg). The 5-HT1A receptors were labelled in total cortex membrane homogenates with [3H]8-OH-DPAT, and the monoamines measured in cingulate cortex by high-performance liquid chromatography. As expected, after pargyline administration tissue concentrations of 5-HT, noradrenaline (NA) and dopamine (DA) were markedly increased due to MAO inhibition with a concomitant decrease of the metabolites 5-hydroxyindole-3-acetic acid and homovanillic acid. However, neither desipramine nor fluoxetine changed monoamine concentrations. Saturation binding with [3H]8-OH-DPAT revealed that, for the control animals (saline treated), the curves were best fitted to a 2-site model. Following drug administration, the saturation curves were still best fitted to a 2-site model, with no changes in affinities or bonding capacities. In competition experiments with 5-HT, buspirone, and pindolol, the curves were always best fitted to a 2-site model. Following fluoxetine administration, the inhibition curves revealed decreases in the affinity of the low-affinity site (KiL) for the agonist buspirone, and in the relative proportion of these sites. In addition, following pargyline, there was an increase in the affinity of the high-affinity site (KiH) for 5-HT but with a decrease of the relative proportion of high-affinity sites. The results confirm that [3H]8-OH-DPAT binding is to a 2-site model, and reveal an absence of downregulation of 5-HT1A receptors following increases in tissue 5-HT after MAO inhibition or antidepressant administrations. Moreover, the data may reflect an alteration of the coupling efficacy between cortical 5-HT1A receptors and their associated G proteins.

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Selected References

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  1. Albert P. R., Zhou Q. Y., Van Tol H. H., Bunzow J. R., Civelli O. Cloning, functional expression, and mRNA tissue distribution of the rat 5-hydroxytryptamine1A receptor gene. J Biol Chem. 1990 Apr 5;265(10):5825–5832. [PubMed] [Google Scholar]
  2. Blier P., De Montigny C. Electrophysiological investigations on the effect of repeated zimelidine administration on serotonergic neurotransmission in the rat. J Neurosci. 1983 Jun;3(6):1270–1278. doi: 10.1523/JNEUROSCI.03-06-01270.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Blier P., de Montigny C. Serotoninergic but not noradrenergic neurons in rat central nervous system adapt to long-term treatment with monoamine oxidase inhibitors. Neuroscience. 1985 Dec;16(4):949–955. doi: 10.1016/0306-4522(85)90107-1. [DOI] [PubMed] [Google Scholar]
  4. Blier P., de Montigny C., Tardif D. Short-term lithium treatment enhances responsiveness of postsynaptic 5-HT1A receptors without altering 5-HT autoreceptor sensitivity: an electrophysiological study in the rat brain. Synapse. 1987;1(3):225–232. doi: 10.1002/syn.890010302. [DOI] [PubMed] [Google Scholar]
  5. Carli M., Anand-Srivastava M. B., Molina-Holgado E., Dewar K. M., Reader T. A. Effects of chronic lithium treatments on central dopaminergic receptor systems: G proteins as possible targets. Neurochem Int. 1994 Jan;24(1):13–22. doi: 10.1016/0197-0186(94)90124-4. [DOI] [PubMed] [Google Scholar]
  6. Chaput Y., de Montigny C., Blier P. Effects of a selective 5-HT reuptake blocker, citalopram, on the sensitivity of 5-HT autoreceptors: electrophysiological studies in the rat brain. Naunyn Schmiedebergs Arch Pharmacol. 1986 Aug;333(4):342–348. doi: 10.1007/BF00500007. [DOI] [PubMed] [Google Scholar]
  7. DeLean A., Munson P. J., Rodbard D. Simultaneous analysis of families of sigmoidal curves: application to bioassay, radioligand assay, and physiological dose-response curves. Am J Physiol. 1978 Aug;235(2):E97–102. doi: 10.1152/ajpendo.1978.235.2.E97. [DOI] [PubMed] [Google Scholar]
  8. Dewar K. M., Grondin L., Nénonéné E. K., Ohayon M., Reader T. A. [3H]paroxetine binding and serotonin content of rat brain: absence of changes following antidepressant treatments. Eur J Pharmacol. 1993 Apr 22;235(1):137–142. doi: 10.1016/0014-2999(93)90833-4. [DOI] [PubMed] [Google Scholar]
  9. Hall M. D., el Mestikawy S., Emerit M. B., Pichat L., Hamon M., Gozlan H. [3H]8-hydroxy-2-(di-n-propylamino)tetralin binding to pre- and postsynaptic 5-hydroxytryptamine sites in various regions of the rat brain. J Neurochem. 1985 Jun;44(6):1685–1696. doi: 10.1111/j.1471-4159.1985.tb07155.x. [DOI] [PubMed] [Google Scholar]
  10. Hamon M., Gozlan H., el Mestikawy S., Emerit M. B., Bolaños F., Schechter L. The central 5-HT1A receptors: pharmacological, biochemical, functional, and regulatory properties. Ann N Y Acad Sci. 1990;600:114–131. doi: 10.1111/j.1749-6632.1990.tb16877.x. [DOI] [PubMed] [Google Scholar]
  11. Juorio A. V., Greenshaw A. J., Wishart T. B. Reciprocal changes in striatal dopamine and beta-phenylethylamine induced by reserpine in the presence of monoamine oxidase inhibitors. Naunyn Schmiedebergs Arch Pharmacol. 1988 Dec;338(6):644–648. doi: 10.1007/BF00165628. [DOI] [PubMed] [Google Scholar]
  12. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  13. Mongeau R., Welner S. A., Quirion R., Suranyi-Cadotte B. E. Further evidence for differential affinity states of the serotonin1A receptor in rat hippocampus. Brain Res. 1992 Sep 11;590(1-2):229–238. doi: 10.1016/0006-8993(92)91100-s. [DOI] [PubMed] [Google Scholar]
  14. Munson P. J., Rodbard D. Ligand: a versatile computerized approach for characterization of ligand-binding systems. Anal Biochem. 1980 Sep 1;107(1):220–239. doi: 10.1016/0003-2697(80)90515-1. [DOI] [PubMed] [Google Scholar]
  15. Nénonéné E. K., Radja F., Carli M., Grondin L., Reader T. A. Heterogeneity of cortical and hippocampal 5-HT1A receptors: a reappraisal of homogenate binding with 8-[3H]hydroxydipropylaminotetralin. J Neurochem. 1994 May;62(5):1822–1834. doi: 10.1046/j.1471-4159.1994.62051822.x. [DOI] [PubMed] [Google Scholar]
  16. Palacios J. M., Waeber C., Hoyer D., Mengod G. Distribution of serotonin receptors. Ann N Y Acad Sci. 1990;600:36–52. doi: 10.1111/j.1749-6632.1990.tb16871.x. [DOI] [PubMed] [Google Scholar]
  17. Peroutka S. J. 5-Hydroxytryptamine receptors. J Neurochem. 1993 Feb;60(2):408–416. doi: 10.1111/j.1471-4159.1993.tb03166.x. [DOI] [PubMed] [Google Scholar]
  18. Radja F., Daval G., Hamon M., Vergé D. Pharmacological and physicochemical properties of pre-versus postsynaptic 5-hydroxytryptamine1A receptor binding sites in the rat brain: a quantitative autoradiographic study. J Neurochem. 1992 Apr;58(4):1338–1346. doi: 10.1111/j.1471-4159.1992.tb11347.x. [DOI] [PubMed] [Google Scholar]
  19. Reader T. A., Dewar K. M. Endogenous homovanillic acid levels differ between rat and rabbit caudate, hippocampus, and cortical regions. Neurochem Res. 1989 Nov;14(11):1137–1141. doi: 10.1007/BF00965620. [DOI] [PubMed] [Google Scholar]
  20. Reader T. A., Grondin L. Distribution of catecholamines, serotonin, and their major metabolites in the rat cingulate, piriform-entorhinal, somatosensory, and visual cortex: a biochemical survey using high-performance liquid chromatography. Neurochem Res. 1987 Dec;12(12):1087–1097. doi: 10.1007/BF00971709. [DOI] [PubMed] [Google Scholar]
  21. Reader T. A., Radja F., Dewar K. M., Descarries L. Denervation, hyperinnervation, and interactive regulation of dopamine and serotonin receptors. Ann N Y Acad Sci. 1995 May 10;757:293–310. doi: 10.1111/j.1749-6632.1995.tb17487.x. [DOI] [PubMed] [Google Scholar]
  22. Ruat M., Traiffort E., Leurs R., Tardivel-Lacombe J., Diaz J., Arrang J. M., Schwartz J. C. Molecular cloning, characterization, and localization of a high-affinity serotonin receptor (5-HT7) activating cAMP formation. Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8547–8551. doi: 10.1073/pnas.90.18.8547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. SPECTOR S., SHORE P. A., BRODIE B. B. Biochemical and pharmacological effects of the monoamine oxidase inhibitors, iproniazid, 1-phenyl-2-hydrazinopropane (JB 516) and 1-phenyl-3-hydrazinobutane (JB 835). J Pharmacol Exp Ther. 1960 Jan;128:15–21. [PubMed] [Google Scholar]
  24. Shen Y., Monsma F. J., Jr, Metcalf M. A., Jose P. A., Hamblin M. W., Sibley D. R. Molecular cloning and expression of a 5-hydroxytryptamine7 serotonin receptor subtype. J Biol Chem. 1993 Aug 25;268(24):18200–18204. [PubMed] [Google Scholar]
  25. Sibley D. R., Creese I. Regulation of ligand binding to pituitary D-2 dopaminergic receptors. Effects of divalent cations and functional group modification. J Biol Chem. 1983 Apr 25;258(8):4957–4965. [PubMed] [Google Scholar]
  26. Stadel J. M., Lefkowitz R. J. Multiple reactive sulfhydryl groups modulate the function of adenylate cyclase coupled beta-adrenergic receptors. Mol Pharmacol. 1979 Nov;16(3):709–718. [PubMed] [Google Scholar]
  27. TAYLOR J. D., WYKES A. A., GLADISH Y. C., MARTIN W. B. New inhibitor of monoamine oxidase. Nature. 1960 Sep 10;187:941–942. doi: 10.1038/187941a0. [DOI] [PubMed] [Google Scholar]
  28. Wong D. T., Horng J. S., Bymaster F. P., Hauser K. L., Molloy B. B. A selective inhibitor of serotonin uptake: Lilly 110140, 3-(p-trifluoromethylphenoxy)-N-methyl-3-phenylpropylamine. Life Sci. 1974 Aug 1;15(3):471–479. doi: 10.1016/0024-3205(74)90345-2. [DOI] [PubMed] [Google Scholar]

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