Psychopharmacology

, Volume 217, Issue 3, pp 377–386 | Cite as

Fluvoxamine enhances prefrontal dopaminergic neurotransmission in adrenalectomized/castrated mice via both 5-HT reuptake inhibition and σ1 receptor activation

  • Yukio Ago
  • Koji Yano
  • Naoki Hiramatsu
  • Kazuhiro Takuma
  • Toshio Matsuda
Original Investigation

Abstract

Rationale

Fluvoxamine, a selective serotonin (5-HT) reuptake inhibitor (SSRI) and an agonist for the σ1 receptors, increases extracellular monoamines in the prefrontal cortex, but it is not known whether the σ1 receptor is involved in the neurochemical effect of fluvoxamine.

Objectives

In view of the fact that circulating steroids exert a tonic modulatory effect on σ1 receptor-mediated effects, the present study examines the effects of fluvoxamine on prefrontal extracellular monoamine levels in adrenalectomized/castrated mice lacking the peripheral sources of steroids.

Results

Fluvoxamine-induced increases in the extracellular levels of dopamine (DA), but not of 5-HT and noradrenaline, were significantly higher in adrenalectomized/castrated than in sham-operated mice, and this effect was blocked by BD1047, a selective σ1 receptor antagonist. In contrast, the effects of paroxetine, an SSRI without affinity for the σ1 receptors, and (+)-SKF-10,047, a selective σ1 receptor agonist, on the extracellular monoamine levels did not differ between adrenalectomized/castrated and sham-operated mice, while the increase in extracellular DA levels induced by co-administration of these drugs was higher in adrenalectomized/castrated than in the control mice. Moreover, fluvoxamine increased c-Fos expression, a marker of neuronal activity, in the prefrontal cortex of adrenalectomized/castrated mice, and this effect was blocked by BD1047. The similar increase in c-Fos expression was observed by co-administration of paroxetine and (+)-SKF-10,047.

Conclusions

These findings suggest that fluvoxamine enhances prefrontal dopaminergic neurotransmission via both 5-HT reuptake inhibition and σ1 receptor activation under the circulating neuroactive steroid-deficient conditions.

Keywords

Fluvoxamine σ1 receptor c-Fos Adrenalectomy/castration Dopamine (DA) Prefrontal cortex 

Supplementary material

213_2011_2293_Fig8_ESM.jpg (68 kb)

Supplementary figure legend Effect of the co-administration of fluvoxamine and (+)-SKF-10,047 on the extracellular levels of 5-HT, NA, and DA in the prefrontal cortex of adrenalectomized/castrated mice. Fluvoxamine (30 mg/kg, i.p.; Flv) alone and in combination with (+)-SKF-10,047 (5 mg/kg, s.c.; SKF) were injected at 0 min (arrow). Data are expressed as the mean ± SEM of four mice. (JPEG 68 kb)

Supplementary figure results

(+)-SKF-10,047 did not affect fluvoxamine (30 mg/kg)-induced increase in DA levels in adrenalectomized/castrated mice. Statistical analysis revealed the main significant effect of time (F8,48 = 37.523, p < 0.0001 for 5-HT; F8,48 = 21.797, p < 0.0001 for NA; F8,48 = 20.744, p < 0.0001 for DA), but not of treatment (F1,6 = 0.264, n.s. for 5-HT; F1,6 = 0.017, n.s. for NA; F1,6 = 0.485, n.s. for DA). There was no significant interaction between the time and treatment (F8,48 = 0.169, n.s. for 5-HT; F8,48 = 0.153, n.s. for NA; F8,48 = 0.408, n.s. for DA).

213_2011_2293_MOESM1_ESM.tiff (8 kb)
High resolution image file (TIFF 7 kb)

References

  1. Ago Y, Koyama Y, Baba A, Matsuda T (2003) Regulation by 5-HT1A receptors of the in vivo release of 5-HT and DA in mouse frontal cortex. Neuropharmacology 45:1050–1056PubMedCrossRefGoogle Scholar
  2. Ago Y, Nakamura S, Baba A, Matsuda T (2005) Sulpiride in combination with fluvoxamine increases in vivo dopamine release selectively in rat prefrontal cortex. Neuropsychopharmacology 30:43–51PubMedCrossRefGoogle Scholar
  3. Ago Y, Nakamura S, Kajita N, Uda M, Hashimoto H, Baba A, Matsuda T (2007) Ritanserin reverses repeated methamphetamine-induced behavioral and neurochemical sensitization in mice. Synapse 61:757–763PubMedCrossRefGoogle Scholar
  4. Ago Y, Arikawa S, Yata M, Yano K, Abe M, Takuma K, Matsuda T (2009) Role of prefrontal dopaminergic neurotransmission in glucocorticoid receptor-mediated modulation of methamphetamine-induced hyperactivity. Synapse 63:7–14PubMedCrossRefGoogle Scholar
  5. Artigas F (2010) The prefrontal cortex: a target for antipsychotic drugs. Acta Psychiatr Scand 121:11–21PubMedCrossRefGoogle Scholar
  6. Barrett-Connor E, von Mühlen D, Laughlin GA, Kripke A (1999) Endogenous levels of dehydroepiandrosterone sulfate, but not other sex hormones, are associated with depressed mood in older women: the Rancho Bernardo Study. J Am Geriatr Soc 47:685–691PubMedGoogle Scholar
  7. Barrot M, Vallée M, Gingras MA, Le Moal M, Mayo W, Piazza PV (1999) The neurosteroid pregnenolone sulphate increases dopamine release and the dopaminergic response to morphine in the rat nucleus accumbens. Eur J Neurosci 11:3757–3760PubMedCrossRefGoogle Scholar
  8. Bermack JE, Debonnel G (2005) The role of sigma receptors in depression. J Pharmacol Sci 97:317–336PubMedCrossRefGoogle Scholar
  9. Berr C, Lafont S, Debuire B, Dartigues JF, Baulieu EE (1996) Relationships of dehydroepiandrosterone sulfate in the elderly with functional, psychological, and mental status, and short-term mortality: a French community-based study. Proc Natl Acad Sci USA 93:13410–13415PubMedCrossRefGoogle Scholar
  10. Bymaster FP, Zhang W, Carter PA, Shaw J, Chernet E, Phebus L, Wong DT, Perry KW (2002) Fluoxetine, but not other selective serotonin uptake inhibitors, increases norepinephrine and dopamine extracellular levels in prefrontal cortex. Psychopharmacology 160:353–361PubMedCrossRefGoogle Scholar
  11. Castro E, Tordera RM, Hughes ZA, Pei Q, Sharp T (2003) Use of Arc expression as a molecular marker of increased postsynaptic 5-HT function after SSRI/5-HT1A receptor antagonist co-administration. J Neurochem 85:1480–1487PubMedCrossRefGoogle Scholar
  12. Cobos EJ, Entrena JM, Nieto FR, Cendán CM, Del Pozo E (2008) Pharmacology and therapeutic potential of sigma1 receptor ligands. Curr Neuropharmacol 6:344–366PubMedCrossRefGoogle Scholar
  13. Corpéchot C, Young J, Calvel M, Wehrey C, Veltz JN, Touyer G, Mouren M, Prasad VVK, Banner C, Sjovall J, Baulieu EE, Robel P (1993) Neurosteroids: 3α-hydroxy-5α-pregnan-20-one and its precursors in the brain, plasma, and steroidogenic glands of male and female rats. Endocrinology 133:1003–1009PubMedCrossRefGoogle Scholar
  14. Del Arco A, Mora F (2009) Neurotransmitters and prefrontal cortex–limbic system interactions: implications for plasticity and psychiatric disorders. J Neural Transm 116:941–952PubMedCrossRefGoogle Scholar
  15. Delgado PL (2000) Depression: the case for a monoamine deficiency. J Clin Psychiatry 61(Suppl 6):7–11PubMedGoogle Scholar
  16. Delgado PL, Moreno FA (2000) Role of norepinephrine in depression. J Clin Psychiatry 61(Suppl 1):5–12PubMedGoogle Scholar
  17. Egashira N, Harada S, Okuno R, Matsushita M, Nishimura R, Mishima K, Iwasaki K, Orito K, Fujiwara M (2007) Involvement of the sigma1 receptor in inhibiting activity of fluvoxamine on marble-burying behavior: comparison with paroxetine. Eur J Pharmacol 563:149–154PubMedCrossRefGoogle Scholar
  18. Franklin KBJ, Paxinos G (1997) The mouse brain in stereotaxic coordinates. Academic, San DiegoGoogle Scholar
  19. George MS, Guidotti A, Rubinow D, Pan B, Mikalauskas K, Post RM (1994) CSF neuroactive steroids in affective disorders: pregnenolone, progesterone, and DBI. Biol Psychiatry 35:775–780PubMedCrossRefGoogle Scholar
  20. Gobert A, Millan MJ (1999) Serotonin (5-HT)2A receptor activation enhances dialysate levels of dopamine and noradrenaline, but not 5-HT, in the frontal cortex of freely-moving rats. Neuropharmacology 38:315–317PubMedCrossRefGoogle Scholar
  21. Hardoy MC, Serra M, Carta MG, Contu P, Pisu MG, Biggio G (2006) Increased neuroactive steroid concentrations in women with bipolar disorder or major depressive disorder. J Clin Psychopharmacol 26:379–384PubMedCrossRefGoogle Scholar
  22. Hashimoto K, Fujita Y, Iyo M (2007) Phencyclidine-induced cognitive deficits in mice are improved by subsequent subchronic administration of fluvoxamine: role of sigma-1 receptors. Neuropsychopharmacology 32:514–521PubMedCrossRefGoogle Scholar
  23. Hayashi T, Su TP (2004) σ-1 receptor ligands: potential in the treatment of neuropsychiatric disorders. CNS Drugs 18:269–284PubMedCrossRefGoogle Scholar
  24. Heinz A, Weingartner H, George D, Hommer D, Wolkowitz OM, Linnoila M (1999) Severity of depression in abstinent alcoholics is associated with monoamine metabolites and dehydroepiandrosterone-sulfate concentrations. Psychiatry Res 89:97–106PubMedCrossRefGoogle Scholar
  25. Hindmarch I, Hashimoto K (2010) Cognition and depression: the effects of fluvoxamine, a sigma-1 receptor agonist, reconsidered. Hum Psychopharmacol 25:193–200PubMedCrossRefGoogle Scholar
  26. Huang M, Ichiwaka J, Li Z, Dai J, Meltzer HY (2006) Augmentation by citalopram of risperidone-induced monoamine release in rat prefrontal cortex. Psychopharmacology 185:274–281PubMedCrossRefGoogle Scholar
  27. Ishikawa M, Ishiwata K, Ishii K, Kimura Y, Sakata M, Naganawa M, Oda K, Miyatake R, Fujisaki M, Shimizu E, Shirayama Y, Iyo M, Hashimoto K (2007) High occupancy of sigma-1 receptors in the human brain after single oral administration of fluvoxamine: a positron emission tomography study using [11C]SA4503. Biol Psychiatry 62:878–883PubMedCrossRefGoogle Scholar
  28. Izumi T, Inoue T, Kitaichi Y, Nakagawa S, Koyama T (2006) Target brain sites of the anxiolytic effect of citalopram, a selective serotonin reuptake inhibitor. Eur J Pharmacol 534:129–132PubMedCrossRefGoogle Scholar
  29. Kitaichi Y, Inoue T, Nakagawa S, Boku S, Kakuta A, Izumi T, Koyama T (2010) Sertraline increases extracellular levels not only of serotonin, but also of dopamine in the nucleus accumbens and striatum of rats. Eur J Pharmacol 647:90–96PubMedCrossRefGoogle Scholar
  30. Kobayashi T, Matsuno K, Murai M, Mita S (1997) σ1 receptor subtype is involved in the facilitation of cortical dopaminergic transmission in the rat brain. Neurochem Res 22:1105–1109PubMedCrossRefGoogle Scholar
  31. Koda K, Ago Y, Cong Y, Kita Y, Takuma K, Matsuda T (2010) Effects of acute and chronic administration of atomoxetine and methylphenidate on extracellular levels of noradrenaline, dopamine and serotonin in the prefrontal cortex and striatum of mice. J Neurochem 114:259–270PubMedGoogle Scholar
  32. Kovács KJ (2008) Measurement of immediate-early gene activation- c-fos and beyond. J Neuroendocrinol 20:665–672PubMedCrossRefGoogle Scholar
  33. Matsumoto M, Togashi H, Mori K, Ueno K, Miyamoto A, Yoshioka M (1999) Characterization of endogenous serotonin-mediated regulation of dopamine release in the rat prefrontal cortex. Eur J Pharmacol 383:39–48PubMedCrossRefGoogle Scholar
  34. Maurice T, Urani A, Phan VL, Romieu P (2001) The interaction between neuroactive steroids and the σ1 receptor function: behavioral consequences and therapeutic opportunities. Brain Res Brain Res Rev 37:116–132PubMedCrossRefGoogle Scholar
  35. Meltzer HY, Huang M (2008) In vivo actions of atypical antipsychotic drug on serotonergic and dopaminergic systems. Prog Brain Res 172:177–197PubMedCrossRefGoogle Scholar
  36. Michael A, Jenaway A, Paykel ES, Herbert J (2000) Altered salivary dehydroepiandrosterone levels in major depression in adults. Biol Psychiatry 48:989–995PubMedCrossRefGoogle Scholar
  37. Narita N, Hashimoto K, Tomitaka S, Minabe Y (1996) Interactions of selective serotonin reuptake inhibitors with subtypes of σ receptors in rat brain. Eur J Pharmacol 307:117–119PubMedCrossRefGoogle Scholar
  38. Nishimura T, Ishima T, Iyo M, Hashimoto K (2008) Potentiation of nerve growth factor-induced neurite outgrowth by fluvoxamine: role of sigma-1 receptors, IP3 receptors and cellular signaling pathways. PLoS ONE 3:e2558PubMedCrossRefGoogle Scholar
  39. Paslakis G, Luppa P, Gilles M, Kopf D, Hamann-Weber B, Lederbogen F, Deuschle M (2010) Venlafaxine and mirtazapine treatment lowers serum concentrations of dehydroepiandrosterone-sulfate in depressed patients remitting during the course of treatment. J Psychiatr Res 44:556–560PubMedCrossRefGoogle Scholar
  40. Phan VL, Su TP, Privat A, Maurice T (1999) Modulation of steroidal levels by adrenalectomy/castration and inhibition of neurosteroid synthesis enzymes affect σ1 receptor-mediated behaviour in mice. Eur J Neurosci 11:2385–2396PubMedCrossRefGoogle Scholar
  41. Phan VL, Urani A, Romieu P, Maurice T (2002) Strain differences in σ1 receptor-mediated behaviours are related to neurosteroid levels. Eur J Neurosci 15:1523–1534PubMedCrossRefGoogle Scholar
  42. Phan VL, Urani A, Sandillon F, Privat A, Maurice T (2003) Preserved sigma11) receptor expression and behavioral efficacy in the aged C57BL/6 mouse. Neurobiol Aging 24:865–881PubMedCrossRefGoogle Scholar
  43. Redrobe JP, Bourin M (1998) Dose-dependent influence of buspirone on the activities of selective serotonin reuptake inhibitors in the mouse forced swimming test. Psychopharmacology 138:198–206PubMedCrossRefGoogle Scholar
  44. Renard CE, Fiocco AJ, Clenet F, Hascoet M, Bourin M (2001) Is dopamine implicated in the antidepressant-like effects of selective serotonin reuptake inhibitors in the mouse forced swimming test? Psychopharmacology 159:42–50PubMedCrossRefGoogle Scholar
  45. Rhodes ME, Li PK, Flood JF, Johnson DA (1996) Enhancement of hippocampal acetylcholine release by the neurosteroid dehydroepiandrosterone sulfate: an in vivo microdialysis study. Brain Res 733:284–286PubMedCrossRefGoogle Scholar
  46. Schüle C, Baghai TC, Eser D, Schwarz M, Bondy B, Rupprecht R (2009) Effects of mirtazapine on dehydroepiandrosterone-sulfate and cortisol plasma concentrations in depressed patients. J Psychiatr Res 43:538–545PubMedCrossRefGoogle Scholar
  47. Sharp JW (1997) Phencyclidine (PCP) acts at σ sites to induce c-fos gene expression. Brain Res 758:51–58PubMedCrossRefGoogle Scholar
  48. Taksande BG, Kotagale NR, Tripathi SJ, Ugale RR, Chopde CT (2009) Antidepressant like effect of selective serotonin reuptake inhibitors involve modulation of imidazoline receptors by agmatine. Neuropharmacology 57:415–424PubMedCrossRefGoogle Scholar
  49. Urani A, Roman FJ, Phan VL, Su TP, Maurice T (2001) The antidepressant-like effect induced by σ1-receptor agonists and neuroactive steroids in mice submitted to the forced swimming test. J Pharmacol Exp Ther 298:1269–1279PubMedGoogle Scholar
  50. Veening JG, Coolen LM, Spooren WJ, Joosten H, van Oorschot R, Mos J, Ronken E, Olivier B (1998) Patterns of c-fos expression induced by fluvoxamine are different after acute vs. chronic oral administration. Eur Neuropsychopharmacol 8:213–226PubMedCrossRefGoogle Scholar
  51. Volonté M, Ceci A, Borsini F (1995) Effect of the 5-hydroxytryptamine3 receptor antagonist itasetron (DAU 6215) on (+)-N-allylnormetazocine-induced dopamine release in the nucleus accumbens and in the corpus striatum of the rat: an in vivo microdialysis study. J Pharmacol Exp Ther 275:358–367PubMedGoogle Scholar
  52. Wolkowitz OM, Reus VI, Roberts E, Manfredi F, Chan T, Raum WJ, Ormiston S, Johnson R, Canick J, Brizendine L, Weingartner H (1997) Dehydroepiandrosterone (DHEA) treatment of depression. Biol Psychiatry 41:311–318PubMedCrossRefGoogle Scholar
  53. Wolkowitz OM, Reus VI, Keebler A, Nelson N, Friedland M, Brizendine L, Roberts E (1999) Double-blind treatment of major depression with dehydroepiandrosterone. Am J Psychiatry 156:646–649PubMedGoogle Scholar
  54. Yaffe K, Ettinger B, Pressman A, Seeley D, Whooley M, Schaefer C, Cummings S (1998) Neuropsychiatric function and dehydroepiandrosterone sulfate in elderly women: a prospective study. Biol Psychiatry 43:694–700PubMedCrossRefGoogle Scholar
  55. Yamada M, Nakao S, Sakamoto S, Takamori Y, Tamura Y, Mochizuki-Oda N (2006) Propofol acts at the sigma-1 receptor and inhibits pentazocine-induced c-Fos expression in the mouse posterior cingulate and retrosplenial cortices. Acta Anaesthesiol Scand 50:875–881PubMedCrossRefGoogle Scholar
  56. Zhang W, Perry KW, Wong DT, Potts BD, Bao J, Tollefson GD, Bymaster FP (2000) Synergistic effects of olanzapine and other antipsychotic agents in combination with fluoxetine on norepinephrine and dopamine release in rat prefrontal cortex. Neuropsychopharmacology 23:250–262PubMedCrossRefGoogle Scholar
  57. Zheng P (2009) Neuroactive steroid regulation of neurotransmitter release in the CNS: action, mechanism and possible significance. Prog Neurobiol 89:134–152PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Yukio Ago
    • 1
  • Koji Yano
    • 1
  • Naoki Hiramatsu
    • 1
  • Kazuhiro Takuma
    • 1
  • Toshio Matsuda
    • 1
    • 2
    • 3
  1. 1.Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical SciencesOsaka UniversitySuitaJapan
  2. 2.Department of Experimental Disease Model, The Osaka-Hamamatsu Joint Research Center for Child Mental Development, Graduate School of MedicineOsaka UniversitySuitaJapan
  3. 3.United Graduate School of Child Development, Osaka University, Kanazawa University and Hamamatsu University School of MedicineOsaka UniversitySuitaJapan

Personalised recommendations