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Pharmacopsychiatry 2003; 36(4): 161-164
DOI: 10.1055/s-2003-41202
Original Paper
© Georg Thieme Verlag Stuttgart · New York

Sub-chronic Treatment Effects of an Extract of Hypericum perforatum (St. John’s Wort, Li 160) on Neuroendocrine Responses to the 5-T2A Agonist, DOI in the Rat

M. Franklin1
  • 1University of Oxford Department of Psychiatry, Warneford Hospital Oxford, UK.
Further Information

Publication History

Received: 5.6.2002 Revised: 9.8.2002

Accepted: 26.9.2002

Publication Date:
07 August 2003 (online)

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Clinical studies have demonstrated the antidepressant efficacy of LI 160 extracts, which is comparable to antidepressants such as imipramine. The study was undertaken to assess the sub-chronic effects of LI 160 extract on plasma corticosterone and prolactin (PRL) responses to the post-synaptic 5-HT2A receptor agonist, 2,5-dimethoxy-4-iodophenyl-2-aminopropane (DOI), in the male rat. Results show that sub-chronic treatment with the LI 160 extract reduced corticosterone and PRL responses to DOI. LI 160 may modify brain 5-HT function in the rat, possibly by reducing the sensitivity of central 5-HT2A receptors. This may be a result of decreased receptor expression, signal transduction or intracellular messengers. These findings could be relevant to the therapeutic efficacy of St. John’s wort.

References

  • 1 Bagdy G and Makara G B. Hypothalamic paraventricular nucleus lesions differentially affect 5-HT1A and 5-HT2 receptor agonist-induced oxytocin, prolactin and corticosterone responses.  Endocrinology. 1994;  134 1127-1131
    CrossrefPubMedSearch in Google Scholar
  • 2 Butterweck V, Korte B, Winterhoff H. Pharmacological and endocrine effect of hypericum perforatum and hypericin after repeated treatment.  Pharmacopsychiatry. 2001;  34(Suppl 1) S2-7
    Thieme ConnectPubMedSearch in Google Scholar
  • 3 Butterweck V, Winterhoff H, Herkenham M. St. John’s wort, hypericin, and imipramine: a comparaitve 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 Psych. 2001;  6 547-564
    CrossrefPubMedSearch in Google Scholar
  • 4 Cowen P J. Serotonin receptor sub-types in depression: evidence from studies in neuroendocrine regulation.  Clin Neuropharmacol. 1993;  16 S6-18
    PubMedSearch in Google Scholar
  • 5 Franklin M, McGavin C, Reed A, Cowen P J. Effect of Hypericum perforatum on salivary cortisol in healthy male volunteers.  J Psychopharmacol. 1998;  30(Suppl) A16
    PubMedSearch in Google Scholar
  • 6 Franklin M, Chi J, McGavin C, Hockney R, Reed A, Campling G, Whale R WR, Cowen P J. Neuroendocrine evidence for dopaminergic actions of Hypericum extract (LI 160) in healthy volunteers.  Biol Psych. 1999;  46 199-202
    PubMedSearch in Google Scholar
  • 7 Franklin M, Chi J, 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(4) 360-363
    PubMedSearch in Google Scholar
  • 8 Franklin M, Cowen P J. Researching the antidepressant actions of Hypericum perforatum (St. John’s wort) in animals and man.  Pharmacopsychiatry. 2001;  34(suppl 1) S29-37
    Thieme ConnectPubMedSearch in Google Scholar
  • 9 Gartside S. The effect of psychotropic drugs on 5-HT-mediated neuroendocrine responses in the rat. PhD Thesis University of Oxford, UK 1991: 120-130
    Search in Google Scholar
  • 10 Greeson J M, Sanford B, Monti D A. St. John’s wort (Hypericum perforatum) a review of the current pharmacological, toxicological and clinical literature.  Psychopharmaol. 2001;  153 402-414
    CrossrefPubMedSearch in Google Scholar
  • 11 Hennessey M, Kellerher D, Spiers J P, Kavanagh P, Back D, Mulcahy F, Feely J. St. John’s wort increases expression of P-glycoprotein: implications for drug interactions.  Brit J Clin Pharm. 2002;  53 75-82
    PubMedSearch in Google Scholar
  • 12 Hypericum Depression Trial Study Group (corresponding author Davidson J RT). Effect of Hypericum perforatum (St. John’s wort) in major depressive disorder. A randomised clinical trial.  JAMA. 2002;  287(14) 1807-1814
    CrossrefPubMedSearch in Google Scholar
  • 13 Kasper S. Hypericum perforatum - a review of clinical studies.  Pharmacopsychiatry. 2001;  34(1) S51-55
    Thieme ConnectPubMedSearch in Google Scholar
  • 14 Leonard B E. Mechanism of action of antidepressants.  CNS drugs. 1995;  4 1-12
    PubMedSearch in Google Scholar
  • 15 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.  BMJ. 1996;  313 253-258
    PubMedSearch in Google Scholar
  • 16 Muller W E, Rolli M, Schaffer C, Hafner U. Effects of hypericum extract (LI 160) in biochemical models of antidepressant activity.  Pharmacopsychiatry. 1997;  30 102-107
    Thieme ConnectPubMedSearch in Google Scholar
  • 17 Muller W E, Singer A, Wonnermann M, Hafner U, Rolli M, Schaffer C. Hyperforin represents the neurotransmitter reuptake inhibiting constituent of hypericum extract.  Pharmacopsychiatry. 1998;  31 16-21
    Thieme ConnectPubMedSearch in Google Scholar
  • 18 Nahrstedt A,Butterweck V. Biologically active and other chemical constituents of the herb of hypericum perforatum.  Pharmacopsychiatry. 1997;  30(suppl) 129-134
    PubMedSearch in Google Scholar
  • 19 Nathan P J. Hypericum perforatum (St. John’s wort): a non-selective re-uptake inhibitor? A review of the recent advances in its pharmacology.  J Psychopharmacol. 2001;  15(suppl) 47-54
    CrossrefPubMedSearch in Google Scholar
  • 20 Nelson D R, Thomas D R, Johnson A M. Pharmacological effects of paroxetine after repeated administration to animals.  Acta Psychiatr Scand. 1989;  350(suppl) 21-23
    PubMedSearch in Google Scholar
  • 21 Perloff M D, von Moltke L L, Stormer E, Shader R I, Greenblatt D J. St. John’s wort: an in vitro analysis of P-glycoprotein induction due to extended exposure.  Brit J Pharmacol. 2001;  134 1601-1608
    CrossrefPubMedSearch in Google Scholar
  • 22 Raap D K, Van de Kar L D. Selective serotonin re-uptake inhibitors and neuroendocrine function.  Life Sciences. 1999;  65(12) 1217-1235
    CrossrefPubMedSearch in Google Scholar
  • 23 Sargent P A, Williamson D J, Cowen P J. Brain 5-HT neurotransmission during paroxetine treatment.  Br J Psychiatry. 1998;  172 49-52
    PubMedSearch in Google Scholar
  • 24 Schule C, Baghai T, Ferrera A, Laakman G. Neuroendocrine effects of hypericum extract WS 5570 in 12 healthy male volunteers.  Pharmacophsychiatry. 2001;  34(1) S127-133
    PubMedSearch in Google Scholar
  • 25 Teufel-Mayer R, Gleitz J. Effects of long-term administration of hypericum extracts on the affinity and density of the central 5-HT1A and 5-HT2a receptors.  Pharmacopsychiatry. 1997;  30 113-116
    PubMedSearch in Google Scholar
  • 26 Van de Kar L D, Javed A, Khang Y, Serres F, Raap D K, Gray T S. 5-HT2A receptors stimulate ACT, corticosterone, oxytocin, renin and prolactin release and activate hypothalamic CRF and oxytocin-expressing cells.  J Neuroscience. 2001;  21(10) 3572-3579
    PubMedSearch in Google Scholar
  • 27 Volz H P. Hypericum: an overview of published therapeutic trials.  Pharmacopsychiat. 1997;  30(suppl) 72-76
    PubMedSearch in Google Scholar
  • 28 Wheatley D. LI 160, an extract of St. John’s wort, versus amitriptyline in mildly to moderately depressed outpatients - a controlled 6-week clinical trial.  Pharmacopsychiatry. 1997;  30(suppl) 77-80
    PubMedSearch in Google Scholar
  • 29 Wonnermann M, Singer B, Siebert B, Muller W E. Evaluation of synaptosomal uptake of most relevant constituents of St. John’s wort.  Pharmacopsychiatry. 2001;  34(suppl1) 148-151
    Thieme ConnectPubMedSearch in Google Scholar

Dr. Mike Franklin

Neurosciences

University Department of Psychiatry

Warneford Hospital

Headington

Oxford OX3 7JX

UK

Email: michael.franklin@psychiatry.ox.ac.uk