medigraphic.com
ISSN 0185-3325 (Print)
Órgano Oficial del Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz

2012, Number 5

<< Back Next >>

Salud Mental 2012; 35 (5)

Participación de las hormonas gonadales en el efecto de los fármacos antidepresivos en la rata macho

Martínez-Mota L, Herrera-Pérez JJ, Olivares NM, Fernández-Guasti A

Language: Spanish
References: 43
Page: 359-366
PDF size: 171.48 Kb.


ABSTRACT

It has been proposed that gonadal hormones participate in regulation of mood and emotion in men as well as in the effect of psychoactive drugs, such as antidepressants. However, evaluation of this type of interactions has been poorly studied in clinic and basic studies. The objective of the present study was to determine the role of gonadal hormones, testosterone (T) and 17β-estradiol (E2), one of its main metabolites, in the effect of two antidepressant drugs: desipramine and fluoxetine. The former is a tricyclic antidepressant that inhibits noradrenaline reuptake in a preferential manner, while the second is a serotonin selective reuptake inhibitor (SSRI) and the most prescribed antidepressant. Behavioral evaluations were conducted in adult male rats, intact or orchidectomized (Orx), treated with T (0-2 mg/rata), E2 (0-40 µg/rata), desipramine (0-20 mg/kg), fluoxetine (0-20 mg/kg) and their combinations. Forced swimming test was used as an animal model to detect antidepressant- like effect induced by treatments, on the basis of its predictive validity. We found that desipramine and fluoxetine produced an antidepressant- like effect in gonadally intact male rats. However, the antidepressant- like effect of both treatments was cancelled in Orx males. Treatment with E2, but not with T, produced antidepressant-like actions in Orx males. Interestingly, treatment with E2 restored the antidepressant- like effect of desipramine and fluoxetine, while supplementation with T only reestablished the antidepressant-like action of desipramine, evidencing that gonadal hormones have a differential participation in regulation of neurotransmitter systems involving in the antidepressant effect. In conclusion, the main testicular androgen T, participates in the expression of the effect of antidepressant drugs, mainly via conversion to its estrogenic metabolite E2. These results give support to the idea that a combined therapy of gonadal hormones and antidepressant drugs may be more convenient to treat depressive disorders in hypogonadal men resistant to conventional antidepressant drugs.


REFERENCES

  1. Margolese HC. The male menopause and mood: testosterone decline and depression in the aging male –Is there a link? J Geriatr Psychiat Neurol 2000;13:93-101.

  2. Seidman SN. Testosterone deficiency and mood in aging men: pathogenic and therapeutic interactions. World J Biol Psychiat 2003;4:14-20.

  3. Seidman SN, Walsh BT. Testosterone and depression in aging men. Am J Geriatr Psychiat 1999;7:18-33.

  4. Yesavage JA, Davidson J, Widrow L, Berger PA. Plasma testosterone levels, depression, sexuality, and age. Biol Psychiat 1985;20:222-225.

  5. Schweiger U, Deuschle M, Weber B, Korner A et al. Testosterone, gonadotropin, and cortisol secretion in male patients with major depression. Psychosom Med 1999;61:292-296.

  6. Vogel W, Klaiber EL, Broverman DM. A comparison of the antidepressant effects of a synthetic androgen (Mesterolone) and amitriptyline in depressed men. J Clin Psychiat 1985;46:6-8.

  7. Wagner GJ, Rabkin JG, Rabkin R. A comparative analysis of standard and alternative antidepressants in the treatment of Human Immunodeficiency Virus patients. Com Psychiat 1996;37:402-408.

  8. O’Connor DB, Archer J, Hair WM, Wu FC. Exogenous testosterone, aggression, and mood in eugonadal and hypogonadal men. Physiol Behav 2002;75:557-566.

  9. Seidman SN, Rabkin JG. Testosterone replacement therapy for hypogonadal men with SSRI-refractory depression. J Affect Dis 1998;48:157-161.

  10. Sharpe RM. The role of oestrogen in the male. TEM 1998; 9:371-377.

  11. Bernardi M, Genadani S, Tagliavini S, Bertolini A. Effects of castration and testosterone in experimental models of depression in mice. Behav Neurosci 1989;103:1148-1150.

  12. Edinger KL, Frye CA. Testosterone’s anti-anxiety and analgesic effects may be due in part to actions of its 5alpha-reduced metabolites in the hippocampus. Psychoneuroendocrinology 2005;30:418-430.

  13. Edinger KL, Lee B, Frye CA. Mnemonic effects of testosterone and its 5alpha-reduced metabolites in the conditioned fear and inhibitory avoidance tasks. Pharmacol Biochem Behav 2004;78:559-568.

  14. Rosellini RA, Svare BV, Rhodes ME, Frye CA. The testosterone metabolite and neurosteroid 3-androstanediol may indicate the effects of testosterone on conditioned place preference. Brain Res Rev 2001;37:162-171.

  15. Frye CA, Park D, Tanaka M, Rosellini R et al. The testosterone metabolite and neurosteroid 3alpha-androstanediol may mediate the effects of testosterone on conditioned place preference. Psychoneuroendocrinology 2001;26:731-750.

  16. Edinger KL, Frye CA. Androgens’ effects to enhance learning may be mediated in part through actions at estrogens receptor-beta in the hippocampus. Neurobiol Learn Mem 2007;87:78-85.

  17. Estrada-Camarena E, Fernández-Guasti A, López-Rubalcava, C. Different estrogenic compounds produce an antidepressant-like effect in the forced swimming test. Neuropsychopharmacology 2003;28:830-838.

  18. Walf AA, Frye CA. Antianxiety and antidepressive behavior produced by physiological estradiol regime may be modulated by hypothalamic- pituitary-adrenal axis activity. Neuropsychopharmacology 2005;30:1288-1301.

  19. Porsolt RD, Le Pichon M, Jalfre M. Depression: a new animal model sensitive to antidepressant treatments. Nature 1977;266:730-732.

  20. Detke MJ, Rickels M, Lucki I. Active behaviors in the rat forced swimming test differently produced by serotonergic and noradrenergic antidepressants. Psychopharmacology 1995;21:66-72.

  21. Martínez-Mota L, Contreras CM, Saavedra M. Progesterone reduces immobility in rats forced to swim. Arch Med Res 1999;30:286-289.

  22. Estrada-Camarena E, Fernández-Guasti A, López-Rubalcava C. Interaction between estrogens and antidepressants in the forced swimming test in rats. Psychopharmacology 2004;173:139-145.

  23. Contreras CM, Martínez-Mota L, Saavedra M. Desipramine restricts estrous cycle oscillations in swimming. Prog Neuropsychopharmacol Biol Psychiat 1998;22:1121-1128.

  24. Putnam SK, Du J, Sato S, Hull EM. Testosterone restoration of copulatory behavior correlates with medial preoptic dopamine release in castrated male rats. Horm Behav 2001;39:216-224.

  25. Herrera-Pérez JJ, Martínez Mota L, Fernández-Guasti A. Aging increases susceptibility to develop anhedonia in male rats. Prog Neuropsychopharmacol Biol Psychiat 2008;32:1798-1803.

  26. Herrera-Pérez JJ, Martínez-Mota L, Chavira R, Fernández-Guasti A. Testosterone prevents but not reverse anhedonia in middle-aged males and lacks an effect on stress vulnerability in young adults. Horm Behav 2012;DOI: 10.1016/jyhbehav.2012.02.015.

  27. Kirby LG, Lucki I. The effect of repeated exposure to forced swimming on extracellular levels of 5-hydroxytryptamine in the rat. Stress 1998;2:251-263.

  28. Kirby LG, Show-Green JM, Davis K, Lucki I. The effect of different stressors on extracellular levels of 5-hydroxytryptamine and 5- hydroxyindoleacetic acid. Brain Res 1997;760:218-230.

  29. Lund TD, Hinds LR, Handa RJ. The androgen 5-dihydrotestosterone and its metabolite 5-androstan-3β,17β-diol inhibit the hypothalamus- pituitary-adrenal response to stress by acting through estrogen receptor β-expressing neurons in the hypothalamus. J Neurosci 2006;26:1448-1456.

  30. Viau V, Meaney MJ. The inhibitory effect of testosterone on hypothalamic- pituitary-adrenal response to stress is mediated by the medial preoptic area. J Neurosci 1996;16:1866-1876.

  31. Shores TJ, Leuner B. Estrogen-mediated effects on depression and memory formation in females. J Affect Dis 2003;74:85-96.

  32. Serova L, Rivkin M, Nakashima A, Sabban EL. Estradiol stimulates gene expression of norepinephrine biosynthetic enzymes in rat locus coeruleus. Neuroendocrinology 2002;75:193-200.

  33. Maharjan S, Serova L, Sabban EL. Transcriptional regulation of tyrosine hydroxylase by estrogen: opposite effects with estrogen receptors alpha and beta and interactions with cyclic AMP. J Neurochem 2005;93:1502-1514.

  34. Skett P, Mod, A, Rafte, J, Sahalin L et al. The effects of gonadectomy and hypophysectomy on the metabolism of imipramine and lidocaine by the liver of male and female rats. Biochem Pharm 1980;29:2759-2762.

  35. Shang Y, Boja JW, Dluzen DE. Castration differentially alters [3H]nisoxetine binding to norepinephrine uptake sites in olfactory bulb and frontal cortex of male rats. Synapse 1999;31:250-255.

  36. 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 1999;63:241-247.

  37. Kakiuchi T, Tsukada H, Fukumoto D, Nishiyama S. Effects of Aging on Serotonin Transporter Availability and its Response to Fluvoxamine in the Living Brain: PET Study with [11C](+)McN5652 and [11C](-)McN5652 in Conscious Monkeys. Synapse 2001;40:170-179.

  38. Cervo L, Samanin R. Evidence that dopamine mechanisms in the nucleus accumbens are selectively involved in the effect of desipramine in the forced swimming test. Neuropharmacology 1987;26:1469-1472.

  39. 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 1999;63:241-247.

  40. Bitar MS, Ota M, Linnoila M, Shapiro BH. Modification of gonadectomy- induced increases in brain monoamine metabolism by steroid hormones in male and female rats. Psychoneuroendocrinology 1991;16:547-557.

  41. Kendall DA, Stancel GM, Enna SJ. The influence of sex hormones on antidepressant-induced alterations in neurotransmitter receptor binding. J Neurosci 1982;2:354-360.

  42. Martínez-Mota L, Cruz Martínez JJ, Márquez-Baltazar MS, Fernández- Guasti A. Estrogens participate in the antidepressant-like effect of desipramine and fluoxetine in male rats. Pharmacol Biochem Behav 2008;88:332-340.

  43. Herrera-Pérez JJ, Martínez-Mota L, Fernández-Guasti A. Aging impairs the antidepressant-like response of citalopram in male rats. Eur J Pharmacol 2010;639:39-43.




2020     |     www.medigraphic.com