Effect of Fluoxetine hydrochloride on the hormonal profile

  • Bhupendra K. Pushkar Department of Biotechnology, University of Mumbai
  • Rohini Sivabalan
Keywords: Hormone, Fluoxetine, Depression

Abstract

While the world if fighting with several diseases and waiting for their complete prognosis, one of the diseases taking centre stage in death drama is depression. Depression is a psychological-physiological disorder involving intense feeling of sadness, lack of energy, feelings of helplessness, hopelessness and despair. Depression affects mood, thoughts, body and work efficiency. By the year 2020, depression will be the 2nd most common health problem in the world (WHO & Harvard University).Fluoxetine (trade name Prozac) is an antidepressant drug belonging to the class of the selective serotonin reuptake inhibitors (SSRI). Fluoxetine is approved for the treatment of major depression, obsessive-compulsive disorder, bulimia nervosa, panic disorder and premenstrual dysphoric disorder. Despite the availability of newer agents, it remains extremely popular due to its reduced side effects as compared to other tricyclics anti-depressants. The two main objectives of the treatment for such a disorder are complete prognosis and avoidance of the relapse. The main aim of the current investigation was to find the efficacy of the drug and test its side effects on the reproductive milieu using the albino rats and extrapolate the results of the same to human. Estimation of hormones related to reproduction in order to find the effect of the drug on Hypothalamus-pituitary-gonadal axis. In all the overall objective of the work was to find the effect of the drug on hormonal levels. 

Author Biography

Bhupendra K. Pushkar, Department of Biotechnology, University of Mumbai
Head of Department, Department of Biotechnology, University of Mumbai, Kalina, Santacruz (E), Mumbai, 400098, Maharashtra, India

References

1. Ryan MC and Paul JP. Depression in Aging Men The Role of Testosterone. Drugs Aging 2004;21(6):361-376.
2. Shores MM, Sloan KL, Matsumoto AM, Moceri VM, Felker B, Kivlahan DR. Increased incidence of diagnosed depressive illness in hypogonadal older men. Arch Gen Psychiatry.2004; 61: 162–7.
3. Shores MM, Moceri VM, Sloan KL, Matsumoto AM, Kivlahan DR. Low testosterone levels predict incident depressive illness in older men: effects of age and medical morbidity. J Clin Psychiatry.2005; 66: 7–14.
4. Sumner BEH, Fink G. Testosterone as well as estrogen increases serotonin2A receptor mRNA and binding site densities in the male rat brain. Mol Brain Res 1998;59:205–214.
5. Fink G, Barbara Sumner, Roberta Rosie, Helen Wilson, Judith McQueen. Androgen actions on central serotonin neurotransmission: relevance for mood, mental state and memory. Behavioural Brain Research 1999;105:53–68.
6. Robichaud M, Debonnel G. Oestrogen and testosterone modulate the firing activity of dorsal raphe nucleus serotonergic neurones in both male and female rats. J Neuroendocrinol2005;17:179–85.
7. Sandrini M, Vergoni AV, Bertolini A. [3H]Imipramine binding in discrete brain areas is affected by castration in male rats. Brain Res 1989; 496: 29–34.
8. Mendelson SD, McEwen BS. Testosterone increases the concentration of [3H]8-hydroxy-2-(di-n-propylamino) tetralin. Binding at 5-HT1A receptors in the medial preoptic nucleus of the castrated male rat.Eur J Pharmacol 1990;181:329–331.
9. Flu¨ gge G, Kramer M, Rensing S, Fuchs E. 5-HT1A-receptors and behaviour under chronic stress: selective counteraction by testosterone. Eur J Neurosci 1998;10:2685–2693.
10. Sundblad C, Eriksson E. Reduced extracellular levels of serotonin in the amygdala of androgenized female rats. EurNeuropsychopharmacol 1997;7:253–259.
11. Cologer-Clifford A, Simon NG, Richter ML, Smoluk SA, Lu S. Androgens and estrogens modulate 5-HT1A and 5-HT1B agonist effects on aggression. PhysiolBehav 1999;65:823–828.
12. Thiblin I, Finn A, Ross SB, Stenfors C. Increased dopaminergic and 5-hydroxytryptaminergic activities in male rat brain following longterm treatment with anabolic androgenic steroids. Br J Pharmacol 1999;126:1301–1306.
13. Mitchell R, Hollist S, Rothwell C, Robertson WR. Age related changes in the pituitary-testicular axis in normal men; lower serum testosterone results from decreased bioactive LH drive. ClinEndocrinol 1995;42:501–7.
14. Vermeulen A. The male climacterium. Ann Med 1993;25:531–4.
15. Zitzmann M and Nieschlag E. Testosterone levels in healthy men and the relation to behavioural and physical characteristics: facts and constructs. Eur J Endocrinol 2001; 144:183-97.
16. Fink G, Sumner BE, McQueen JK, Wilson H, Rosie R. Sex steroid control of mood, mental state and memory. Clin-ExpPharmacolPhysiol1998;25:764–775.
17. Shors TJ, Leuner B. Estrogen-mediated effects on affect and memory formation. Journal of Affective Disorders 2003; 74:85-96.
18. McQueen JK, Wilson H, Fink G. Estradiol-17 beta increases serotonin transporter (SERT) mRNA levels and the density of SERT-binding sites in female rat brain. Brain Res Mol Brain Res 1997;45:13–23.
19. McQueen JK, Wilson H, Sumner BE, Fink G. Serotonin transporter (SERT) mRNA and binding site densities in male rat brain affected by sex steroids. Brain Res Mol Brain Res 1999;63:241–247.
20. George K, Aghajanian and Gerard J Marek, Sero-tonin–Glutamate Interactions: A New Target for Antipsy-chotic Drugs, Neuropsychopharmacology (1999) 21, S122–S133.
21. Fink G. The GW Harris Lecture.Steroid control of brain and pituitary function. Q J ExpPhysiol 1988;73:257–93.
22. Herbison AE. Multimodal influence of estrogen upon gonadotropin-releasing hormone neurons.Endocr Rev 1998;19:302–30.
23. Graziano P, Roberto C, Agis-Balboa, Fabio P, Marianela N, Alessandro G, Erminio C. Neurosteroid Biosynthesis Regulates Sexually Dimorphic Fear and Aggressive Behavior in Mice. Neurochem Res 2008;33:1990–2007
24. Gary ED, Darin JK, Stanley WC, George RB. Differential Effects of Chronic Antidepressant Treatment on Swim Stress and Fluoxetine-Induced Secretion of Corticosterone and Progesterone. Pharmacology and experimental therapeutics 1998;285:(2):579-587.
25. Pinna G, Uzunova V, Matsumoto K, Puia G, Mienville J-M, Costa E, Guidotti A. Brain allopregnanolone regulates the potency of the GABAA receptor agonist muscimol. Neuropharmacology 2000;39:440–448.
26. Puia G, Mienville JM, Matsumoto K, Takahata H, Watanabe H, Costa E, Guidotti A. On the putative physiological role of allopregnanolone on GABAA receptor function. Neuropharmacology 2003;44:49–55.
27. Belelli D, Lambert JJ. Neurosteroids: endogenous regulators of the GABAA receptor. Nat Rev Neurosci 2005;6:565–575.
28. Toshiro N,Kazushi O,Toyoko H,Susumu I, Shizuo N, Yoshihiko F. Effect of Psychotropic Drugs on the 21-Hydroxylation of Neurosteroids, Progesterone and Allopregnanolone, Catalyzed by Rat CYP2D4 and Human CYP2D6 in the Brain. BiolPharmBull 2008;31(3):348-351.
29. Pinna G, Costa E, Guidotti A. Fluoxetine and norfluoxetinestereospecifically and selectively increase brain neurosteroid content at doses that are inactive on 5-HT reuptake.Psychopharmacology (Berl) 2006;186:362–372.
30. Rasmusson AM, Pinna G, Paliwal P, Weisman D, Gottshalk C, Charney D, Krystal J, Guidotti A. Decreased cerebrospinal fluid allopregnanolone levels in women with posttraumatic stress disorder. Biol Psychiatry 2006;60:704–713.
31. Uzunova V, Sheline Y, Davis JM, Rasmusson A, Uzunov DP, Costa E, Guidotti A. Increase in the cerebrospinal fluid content of neurosteroids in patients with unipolar major depression who are receiving fluoxetine or fluvoxamine. ProcNatlAcadSci USA 1998;95:3239–3244.
32. Uzunova V, Sampson L, Uzunov DP. Relevance of endogenous 3a-reduced neurosteroids to depression and antidepressant action. Psychopharmacology (Berl) 2006;186:351-361.
33. Dudely RA, et al. Guidelines for immunoassay data reduction. ClinChem 1985;31:1264-71.
34. Anderson DT, Fritz KL, Muto JJ. Distribution of mirtazapine (Remeron) in thirteen postmortem cases. J Anal Toxicol 1999;23:544–548.
35. Christian K, Lang M, Maurel P, Raffalli-Mathieu F. Interaction of heterogenous nuclear ribonucleoprotein A1 with cytochrome P450 2A6 mRNA: Implications for post-transcriptional regulation of the CYP2A6 gene. Mol-Pharmacol 2004;65:1405–1414.
36. Daniel WA, Haduch A, Wójcikowski J. Inhibition and possible induction of rat CYP2D after short- and longterm treatment with antidepressants. J Pharm Pharmacol 2002;54:1545–1552.
37. Unnikrishnan G. Effects of Antidepressants in Rats. Thesis submitted to the University of Mumbai 2002.
38. Jørgensen HS. Studies on the neuroendocrine role of serotonin.Dan Med Bull 2007;54:266-88.
39. Fabbri A, Tinajero JC, Dufau ML. Corticotropin-releasing factor is produced by rat Leydig cells and has a major local antigonadotropic role in the testis. Endocrinology 1990;127:1541-1543.
40. Norman RL, Smith CJ. Restraint inhibits luteinizing hormone and testosterone secretion in intact male rhesus macaques: effects of concurrent naloxone administration. Neuroendocrinology 1992;55:405-415.
41. Biver F, Wikler D, Lotstra F, Damhaut P, Goldman S, Mendlewicz J. Serotonin 5-HT2A receptor imaging in major depression: focal changes in orbito-insular cortex. Br J Psychiatry 1997;171:444–8.
42. Deakin JFW. 5-HT2 receptors, depression and anxiety. PharmacolBiochemBehav 1988;29:819–20.
43. Sibille E, Sarnyai Z, Benjamin D, Gal J, Baker H, Toth M. Antisense inhibition of 5-hydroxytryptamine2A receptor induces an antidepressant like effect in mice. MolPharmacol 1997;52:1056–63.
44. Rosier A, Dupont P, Peuskens J, Bormans G, Vandenberghe R, Maes M, de Groot T, Chiepers C, Verbruggen A, Mortelmans L. Visualisation of loss of 5-HT2A receptors with age in healthy volunteers using [18F] altanserin and positron emission tomographic imaging. Psychiatry Res 1996;68:11–2.
45. Fink G, Sumner BEH. Oestrogen and mental state. Nature 1996;383:306.
46. Sumner BEH, Fink G. Effects of acute estradiol on 5-hydroxytryptamine and dopamine receptor subtype mRNA expression in female rat brain. Mol Cell Neurosci 1993;4:83–92.
47. Sumner BEH, Fink G. Estrogen increases the density of 5-hydroxytryptamine2A receptors in cerebral cortex and nucleus accumbens in the female rat. J Steroid BiochemMolBiol 1995;54:15-20.
48. Sumner BEH, Fink G. The density of 5-hydroxytryptamine2A receptors in forebrain is increased at pro-estrus in intact female rats. NeurosciLett 1997;234:7–10.
49. Halbreich U, Endicott J, Goldstein S, Nee J. Premenstrual changes and changes in gonadal hormones. ActaPsychiatrScand 1986;74:576–86.
50. Reid RL, Yen SSC. Premenstrual syndrome. Am J ObstetGynecol 1981;139:85–104.
51. Studd J, Zamblera D. Premenstrual depression. Focus Depr 1994;2:6–9.
52. Halbreich U, Rojansky N, Palter S, Tworek H, Hissin P, Wang K. Estrogen augments serotonergic activity in postmenopausal women. Biol Psychiatry 1995;37:434–41.
53. Hay AG, Bancroft J, Johnstone EC. Affective symptoms in women attending a menopause clinic. Br J Psychiatry 1994;164:513–6.
54. Nicol-Smith L. Causality, menopause, and depression: a critical review of the literature. Br Med J 1996;313:1229–32.
55. Pearlstein T, Rosen K, Stone AB. Mood disorders and menopause. EndocrinolMetabClin North Am 1997;26:279–94.
56. Rocha BA, Fleischer R, Schaeffer JM, Rohrer SP, Hickey GJ. 17 Beta-estradiol-induced antidepressant-like effect in the forced swim test is absent in estrogen receptor-beta knockout (BERKO) mice. Psychopharmacology (Berl) 2005;179:637–643.
57. Michael J. Weiser, Chad D. Foradori, and Robert J. Handa.Estrogen Receptor Beta in the Brain: From Form to Function. Brain res rev 2008;57(2):309-320.
58. Wu FS, Gibbs TT, Farb DH. Inverse modulation of gamma-aminobutyric acid- and glycine-induced currents by progesterone.MolPharmacol 1990;37(5):597-602.
59. Jung-Testas I, Do Thi A, Koenig H, Desarnaud F, Shazand K, Schumacher M, Baulieu EE. J. Steroid Biochem. Mol. Biol 1999;69:97—107.
60. Paul SM, Purdy RH. Neuroactive steroids.FASEB J 1992;6:2311—2322.
61. Toshiro N,Kazushi O,Toyoko H,Susumu I, Shizuo N, Yoshihiko F. Effect of Psychotropic Drugs on the 21-Hydroxylation of Neurosteroids, Progesterone and Allopregnanolone, Catalyzed by Rat CYP2D4 and Human CYP2D6 in the Brain. BiolPharmBull 2008;31(3):348-351
Published
2015-03-29
Section
Original Article