PDF herunterladen
Horm Metab Res 2003; 35(10): 602-606
DOI: 10.1055/s-2003-43507
Original Clinical
© Georg Thieme Verlag Stuttgart · New York

The Prototypic Antidepressant Drug, Imipramine, but not Hypericum perforatum (St. John’s Wort), Reduces HPA-Axis Function in the Rat

P.  Frost 1 , S.  Bornstein 2 , M.  Ehrhart-Bornstein 2 , F.  O’Kirwan 1 , C.  Hutson 1 , D.  Heber 3 , V.  Go 3 , J.  Licinio 1 , M.-L.  Wong 1
  • 1Laboratory of Pharmacogenomics, Neuropsychiatric Institute, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
  • 2Department of Endocrinology, Heinrich-Heine University, Dusseldorf, Germany
  • 3Center for Dietary Supplement Research Botanicals, UCLA Center for Human Nutrition, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
Weitere Informationen

Publikationsverlauf

Received 5 August 2002

Accepted after second revision 7 May 2003

Publikationsdatum:
07. November 2003 (online)

Auch verfügbar auf
    Lizenzen und Reprints

Abstract

Dysregulation in corticotropin-releasing hormone (CRH) secretion in the hypothalamus-pituitary-adrenal (HPA) axis may be involved in the etiology of major depressive disorder (MDD). Chronic therapy with standard antidepressant drugs, such as imipramine, can downregulate HPA axis function, indicating that the HPA axis may be an important target for antidepressant action. We tested several doses of a standardized commercial preparation of Hypericum perforatum plant extract (popularly known as St. John’s Wort), a medicinal herb used for treating mild depressive symptoms, to determine whether it also modulated HPA axis function. Chronic imipramine treatment (daily injections for 8 weeks) of male Sprague-Dawley rats significantly downregulated circulating plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone compared to animals treated with saline. However, chronic St. John’s Wort treatment (daily gavage for 8 weeks) had no effect on plasma ACTH or corticosterone, even at the highest doses tested. Our results confirm previous findings that imipramine may have significant peripheral HPA axis-mediated effects. However, our data does not support any role for H. perforatum in modulation of HPA axis function, suggesting that alternative pathways may be involved in mediating its antidepressant effects.

Key words

Major depressive disorder · Stress · ACTH · Corticosterone

References

  • 1 Regier D A, Narrow W E, Rae D S, Manderscheid R W, Locke B Z, Goodwin F K. The de facto US mental and addictive disorders service system. Epidemiologic catchment area prospective 1-year prevalence rates of disorders and services.  Arch Gen Psychiatry. 1993;  50 85-94
    CrossrefPubMedGoogle Scholar
  • 2 Keith S J, Matthews S M. The value of psychiatric treatment: its efficacy in severe mental disorders.  Psychopharmacol Bull. 1993;  29 427-430
    PubMedGoogle Scholar
  • 3 Moller H J, Volz H P. Drug treatment of depression in the 1990s. An overview of achievements and future possibilities.  Drugs. 1996;  52 625-638
    PubMedGoogle Scholar
  • 4 Broekkamp C L, Leysen D, Peeters B W, Pinder R M. Prospects for improved antidepressants.  J Med Chem. 1995;  38 4615-4633
    CrossrefPubMedGoogle Scholar
  • 5 Bilia A R, Gallori S, Vincieri F F. St. John’s wort and depression. Efficacy, safety and tolerability-an update.  Life Sci. 2002;  70 3077-3096
    CrossrefPubMedGoogle Scholar
  • 6 Linde K, Ramirez G, Mulrow C D, Pauls A, Weidenhammer W, Melchart D. St John’s wort for depression - an overview and meta-analysis of randomised clinical trials [see comments].  Bmj. 1996;  313 253-258
    PubMedGoogle Scholar
  • 7 Whiskey E, Werneke U, Taylor D. A systematic review and meta-analysis of Hypericum perforatum in depression: a comprehensive clinical review.  Int Clin Psychopharmacol. 2001;  16 239-252
    PubMedGoogle Scholar
  • 8 Muller W E, Rolli M, Schafer C, Hafner U. Effects of Hypericum extract (LI 160) in biochemical models of antidepressant activity.  Pharmacopsychiatry. 1997;  2 102-107
    PubMedGoogle Scholar
  • 9 Muller W E, Singer A, Wonnemann M, Hafner U, Rolli M, Schafer C. Hyperforin represents the neurotransmitter reuptake inhibiting constituent of hypericum extract.  Pharmacopsychiatry. 1998;  1 16-21
    PubMedGoogle Scholar
  • 10 Neary J T, Bu Y. Hypericum LI 160 inhibits uptake of serotonin and norepinephrine in astrocytes.  Brain Res. 1999;  816 358-363
    CrossrefPubMedGoogle Scholar
  • 11 Wirz A, Simmen U, Heilmann J, Calis I, Meier B, Sticher O. Bisanthraquinone glycosides of Hypericum perforatum with binding inhibition to CRH-1 receptors.  Phytochemistry. 2000;  55 941-947
    CrossrefPubMedGoogle Scholar
  • 12 Butterweck V, Winterhoff H, Herkenham M. St John’s wort, hypericin, and imipramine: a comparative analysis of mRNA levels in brain areas involved in HPA axis control following short- term and long-term administration in normal and stressed rats.  Mol Psychiatry. 2001;  6 547-564
    CrossrefPubMedGoogle Scholar
  • 13 Butterweck V, Korte B, Winterhoff H. Pharmacological and endocrine effects of Hypericum perforatum and hypericin after repeated treatment.  Pharmacopsychiatry 34 Suppl. 2001;  1 S2-7
    PubMedGoogle Scholar
  • 14 Franklin M, Chi J D, Mannel M, Cowen P J. Acute effects of LI 160 (extract of Hypericum perforatum, St John’s wort) and two of its constituents on neuroendocrine responses in the rat.  J Psychopharmacol. 2000;  14 360-363
    PubMedGoogle Scholar
  • 15 Franklin M, Cowen P J. Researching the antidepressant actions of Hypericum perforatum (St. John’s wort) in animals and man.  Pharmacopsychiatry 34 Suppl. 2001;  1 S29-37
    PubMedGoogle Scholar
  • 16 Brady L S, Whitfield H J, Jr., Fox R J, Gold P W, Herkenham M. Long-term antidepressant administration alters corticotropin-releasing hormone, tyrosine hydroxylase, and mineralocorticoid receptor gene expression in rat brain. Therapeutic implications.  J Clin Invest. 1991;  87 831-837
    CrossrefPubMedGoogle Scholar
  • 17 Brady L S, Gold P W, Herkenham M, Lynn A B, Whitfield H J, Jr.. The antidepressants fluoxetine, idazoxan and phenelzine alter corticotropin-releasing hormone and tyrosine hydroxylase mRNA levels in rat brain: therapeutic implications.  Brain Res. 1992;  572 117-125
    CrossrefPubMedGoogle Scholar
  • 18 Wong M L, Khatri P, Licinio J, Esposito A, Gold P W. Identification of hypothalamic transcripts upregulated by antidepressants.  Biochem Biophys Res Commun. 1996;  229 275-279
    CrossrefPubMedGoogle Scholar
  • 19 Kasper S. Hypericum perforatum - a review of clinical studies.  Pharmacopsychiatry 34 Suppl. 2001;  1 S51-55
    PubMedGoogle Scholar
  • 20 Manji H K, Drevets W C, Charney D S. The cellular neurobiology of depression.  Nat Med. 2001;  7 541-547
    CrossrefPubMedGoogle Scholar
  • 21 Kaehler S T, Sinner C, Chatterjee S S, Philippu A. Hyperforin enhances the extracellular concentrations of catecholamines, serotonin and glutamate in the rat locus coeruleus [In Process Citation].  Neurosci Lett. 1999;  262 199-202
    CrossrefPubMedGoogle Scholar
  • 22 Gold P W. Stress-responsive neuromodulators.  Biol Psychiatry. 1988;  24 371-374
    CrossrefPubMedGoogle Scholar
  • 23 Inder W J, Prickett T C, Mulder R T, Donald R A, Joyce P R. Reduction in basal afternoon plasma ACTH during early treatment of depression with fluoxetine.  Psychopharmacology (Berl). 2001;  156 73-78
    CrossrefPubMedGoogle Scholar
  • 24 Chatterjee S S, Bhattacharya S K, Wonnemann M, Singer A, Muller W E. Hyperforin as a possible antidepressant component of hypericum extracts.  Life Sci. 1998;  63 499-510
    CrossrefPubMedGoogle Scholar
  • 25 Butterweck V, Wall A, Liefländer-Wulf U, Winterhoff H, Nahrstedt A. Effects of the total extract and fractions of Hypericum perforatum in animal assays for antidepressant activity.  Pharmacopsychiatry 30 Suppl. 1997;  2 117-124
    PubMedGoogle Scholar

M.-L. Wong, M. D.

3357 Gonda Center

695 Charles Young Dr, So., Los Angeles · CA. 90095-1761 · USA ·

Telefon: + 1-310-825-7113

Fax: + 1-310-206-6715

eMail: mali@ucla.edu