The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Fluoxetine Modulates Corticostriatal Synaptic Transmission through Postsynaptic Mechanism

  • Cho, Hyeong-Seok (Deportment of Pharmacology, MRC for Cell neath Disease Research Center, College of Medicine, The Catholic University of Korea) ;
  • Choi, Se-Joon (Deportment of Pharmacology, MRC for Cell neath Disease Research Center, College of Medicine, The Catholic University of Korea) ;
  • Kim, Ki-Jung (Deportment of Pharmacology, MRC for Cell neath Disease Research Center, College of Medicine, The Catholic University of Korea) ;
  • Lee, Hyun-Ho (Deportment of Pharmacology, MRC for Cell neath Disease Research Center, College of Medicine, The Catholic University of Korea) ;
  • Cho, Young-Jin (Deportment of Pharmacology, MRC for Cell neath Disease Research Center, College of Medicine, The Catholic University of Korea) ;
  • Kim, Seong-Yun (Deportment of Pharmacology, MRC for Cell neath Disease Research Center, College of Medicine, The Catholic University of Korea) ;
  • Sung, Ki-Wug (Deportment of Pharmacology, MRC for Cell neath Disease Research Center, College of Medicine, The Catholic University of Korea)
  • Published : 2006.02.21
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Abstract

Fluoxetine, widely used for the treatment of depression, is known to be a selective serotonin reuptake inhibitor (SSRI), however, there are also reports that fluoxetine has direct effects on several receptors. Employing whole-cell patch clamp techniques in rat brain slice, we studied the effects of fluoxetine on corticostriatal synaptic transmission by measuring the change in spontaneous excitatory postsynaptic currents (sEPSC). Acute treatment of rat brain slice with fluoxetine ($10{\mu}M$) significantly decreased the amplitude of sEPSC ($8.1{\pm}3.3$%, n=7), but did not alter its frequency ($99.1{\pm}4.7$%, n=7). Serotonin ($10{\mu}M$) also significantly decreased the amplitude ($81.2{\pm}3.9$%, n=4) of sEPSC, but did not affect its frequency ($105.8{\pm}8.0$, n=4). The effect of fluoxetine was found to have the same trend as that of serotonin. We also found that the inhibitory effect of fluoxetine on sEPSC amplitude ($93.0{\pm}1.9$%, n=8) was significantly blocked, but not serotonin ($84.3{\pm}1.6$%, n=4), when the brain slice was incubated with p-chloroamphetamine ($10{\mu}M$), which depletes serotonin from the axon terminals and blocks its reuptake. These results suggest that fluoxetine inhibits corticostriatal synaptic transmission through postsynaptic, and that these effects are exerted through both serotonin dependent and independent mechanism.

Keywords

References

  1. Barnes NM, Sharp T. A review of central 5-HT receptors and their function. Neuropharmacology 38: 1083-1152, 1999 https://doi.org/10.1016/S0028-3908(99)00010-6
  2. Bennett MR, Kearns JL. Statistics of transmitter release at nerve terminals. Prog Neurobiol 60: 545-606, 2000 https://doi.org/10.1016/S0301-0082(99)00040-4
  3. Cho HS, Choi SJ, Kim KJ, Lee HH, Kim SY, Cho YJ, Sung KW. 5-hydroxytryptamine inhibits glutamatergic synaptic transmission in rat corticostriatal brain slice. Korean J Physiol Pharmacol 9: 255-262, 2005
  4. Choi JS, Choi BH, Ahn HS, Kim MJ, Rhie DJ, Yoon SH, Min do S, Jo YH, Kim MS, Sung KW, Hahn SJ. Mechanism of block by fluoxetine of 5-hydroxytryptamine3 (5-HT3)-mediated currents in NCB-20 neuroblastoma cells. Biochem Pharmacol 66: 2125-2132, 2003 https://doi.org/10.1016/j.bcp.2003.08.012
  5. Choi SJ, Chung WS, Kim KJ, Sung KW. Inhibitory modulation of 5-hydroxytryptamine on corticostriacal synaptic transmission in rat brain slice. Korean J Physiol Pharmacol 7: 295-301, 2003
  6. Cusack B, Nelson A, Richelson E. Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl) 114: 559-565, 1994 https://doi.org/10.1007/BF02244985
  7. Deak F, Lasztoczi B, Pacher P, Petheo GL, Valeria K, Spat A. Inhibition of voltage-gated calcium channels by fluoxetine in rat hippocampal pyramidal cells. Neuropharmacology 39: 1029-1036, 2000 https://doi.org/10.1016/S0028-3908(99)00206-3
  8. Garcia-Colunga J, Awad JN, Miledi R. Blockage of muscle and neuronal nicotinic acetylcholine receptors by fluoxetine (Prozac). Proc Natl Acad Sci USA 94: 2041-2044, 1997
  9. Hahn SJ, Choi JS, Rhie DJ, Oh CS, Jo YH, Kim MS. Inhibition by fluoxetine of voltage-activated ion channels in rat PC12 cells. Eur J Pharmacol 367: 113-118, 1999 https://doi.org/10.1016/S0014-2999(98)00955-8
  10. Jones BJ, Blackburn TP. The medical benefit of 5-HT research. Pharmacol Biochem Behav 71: 555-568, 2002 https://doi.org/10.1016/S0091-3057(01)00745-6
  11. Kirby LG, Lucki I. Interaction between the forced swimming test and fluoxetine treatment on extracellular 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in the rat. J Pharmacol Exp Ther 282: 967-976, 1997
  12. Koch S, Perry KW, Bymaster FP. Brain region and dose effects of an olanzapine/fluoxetine combination on extracellular monoamine concentrations in the rat. Neuropharmacology 46: 232- 242, 2004 https://doi.org/10.1016/j.neuropharm.2003.09.001
  13. Muramatsu M, Lapiz MD, Tanaka E, Grenhoff J. Serotonin inhibits synaptic glutamate currents in rat nucleus accumbens neurons via presynaptic 5-HT1B receptors. Eur J Neurosci 10: 2371- 2379, 1998 https://doi.org/10.1046/j.1460-9568.1998.00248.x
  14. Page ME, Detke MJ, Dalvi A, Kirby LG, Lucki I. Serotonergic mediation of the effects of fluoxetine, but not desipramine, in the rat forced swimming test. Psychopharmacology (Berl) 147: 162-167, 1999 https://doi.org/10.1007/s002130051156
  15. Pancrazio JJ, Kamatchi GL, Roscoe AK, Lynch C 3rd. Inhibition of neuronal Na+ channels by antidepressant drugs. J Pharmacol Exp Ther 284: 208-214, 1998
  16. Porsolt RD, Le Pichon M, Jalfre M. Depression: a new animal model sensitive to antidepressant treatments. Nature 266: 730-732, 1977 https://doi.org/10.1038/266730a0
  17. Porsolt RD, Anton G, Blavet N, Jalfre M. Behavioural despair in rats: a new model sensitive to antidepressant treatments. Eur J Pharmacol 47: 379-391, 1978 https://doi.org/10.1016/0014-2999(78)90118-8
  18. Robinson RT, Drafts BC, Fisher JL. Fluoxetine increases GABA(A) receptor activity through a novel modulatory site. J Pharmacol Exp Ther 304: 978-984, 2003 https://doi.org/10.1124/jpet.102.044834
  19. Ronesi J, Lovinger DM. Induction of striatal long-term synaptic depression by moderate frequency activation of cortical afferents in rat. J Physiol 562: 245-256, 2005 https://doi.org/10.1113/jphysiol.2004.068460
  20. Sands SA, Reisman SA, Enna SJ. Effect of antidepressants on GABA(B) receptor function and subunit expression in rat hippocampus. Biochem Pharmacol 68: 1489-1495, 2004 https://doi.org/10.1016/j.bcp.2004.07.027
  21. Scholze P, Zwach J, Kattinger A, Pifl C, Singer EA, Sitte HH. Transporter-mediated release: a superfusion study on human embryonic kidney cells stably expressing the human serotonin transporter. J Pharmacol Exp Ther 293: 870-878, 2000
  22. Slattery DA, Desrayaud S, Cryan JF. GABAB receptor antagonistmediated antidepressant-like behavior is serotonin-dependent. J Pharmacol Exp Ther 312: 290-296, 2005 https://doi.org/10.1124/jpet.104.073536
  23. Sprague JE, Johnson MP, Schmidt CJ, Nichols DE. Studies on the mechanism of p-chloroamphetamine neurotoxicity. Biochem Pharmacol 52: 1271-1277, 1996 https://doi.org/10.1016/0006-2952(96)00482-0
  24. Sung KW, Choi S, Lovinger DM. Activation of group I mGluRs is necessary for induction of long-term depression at striatal synapses. J Neurophysiol 86: 2405-2412, 2001 https://doi.org/10.1152/jn.2001.86.5.2405
  25. Svenningsson P, Tzavara ET, Witkin JM, Fienberg AA, Nomikos GG, Greengard P. Involvement of striatal and extrastriatal DARPP- 32 in biochemical and behavioral effects of fluoxetine (Prozac). Proc Natl Acad Sci USA 99: 3182-3187, 2002
  26. Svenningsson P, Nishi A, Fisone G, Girault JA, Nairn AC, Greengard P. DARPP-32: an integrator of neurotransmission. Annu Rev Pharmacol Toxicol 44: 269-296, 2004 https://doi.org/10.1146/annurev.pharmtox.44.101802.121415
  27. Tunnicliff G, Schindler NL, Crites GJ, Goldenberg R, Yochum A, Malatynska E. The GABA(A) receptor complex as a target for fluoxetine action. Neurochem Res 24: 1271-1276, 1999 https://doi.org/10.1023/A:1020977123968
  28. Tytgat J, Maertens C, Daenens P. Effect of fluoxetine on a neuronal, voltage-dependent potassium channel (Kv1.1). Br J Pharmacol 122: 1417-1424, 1997 https://doi.org/10.1038/sj.bjp.0701545
  29. Wong DT, Bymaster FP, Engleman EA. Prozac (fluoxetine, Lilly 110140), the first selective serotonin uptake inhibitor and an antidepressant drug: twenty years since its first publication. Life Sci 57: 411-441, 1995 https://doi.org/10.1016/0024-3205(95)00209-O
  30. Yakel JL, Trussell LO, Jackson MB. Three serotonin responses in cultured mouse hippocampal and striatal neurons. J Neurosci 8: 1273-1285, 1988 https://doi.org/10.1523/JNEUROSCI.08-04-01273.1988