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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

Molecular Psychiatry volume 6, pages 547–564 (2001)Cite this article

Abstract

Clinical studies demonstrate that the antidepressant efficacy of St John's wort (Hypericum) is comparable to that of tricyclic antidepressants such as imipramine. Onset of efficacy of these drugs occurs after several weeks of treatment. Therefore, we used in situhybridization histochemistry to examine in rats the effects of short-term (2 weeks) and long-term (8 weeks) administration of imipramine, Hypericum extract, and hypericin (an active constituent of St John's wort) on the expression of genes that may be involved in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Imipramine (15 mg kg−1), Hypericum (500 mg kg−1), and hypericin (0.2 mg kg−1) given daily by gavage for 8 weeks but not for 2 weeks significantly decreased levels of corticotropin-releasing hormone (CRH) mRNA by 16–22% in the hypothalamic paraventricular nucleus (PVN) and serotonin 5-HT1A receptor mRNA by 11–17% in the hippocampus. Only imipramine decreased tyrosine hydroxylase (TH) mRNA levels in the locus coeruleus (by 23%), and only at 8 weeks. The similar delayed effects of the three compounds on gene transcription suggests a shared action on the centers that control HPA axis activity. A second study was performed to assess the effects of long-term imipramine and Hypericum administration on stress-induced changes in gene transcription in stress-responsive circuits. Repeated immobilization stress (2 h daily for 7 days) increased mRNA levels of CRH in the PVN, proopiomelanocortin (POMC) in the anterior pituitary, glutamic acid decarboxylase (GAD 65/67) in the bed nucleus of the stria terminalis (BST), cyclic AMP response element binding protein (CREB) in the hippocampus, and TH in the locus coeruleus. It decreased mRNA levels of 5-HT1A and brain-derived neurotrophic factor (BDNF) in the hippocampus. Long-term pre-treatment with either imipramine or Hypericum reduced to control levels the stress-induced increases in gene transcription of GAD in the BST, CREB in the hippocampus, and POMC in the pituitary. The stress-induced increases in mRNA levels of CRH in the PVN and TH in the locus coeruleus were reduced by imipramine but not by Hypericum. The stress-induced decreases in BDNF and 5-HT1AmRNA levels were not prevented by either drug. Taken together, these data show: (1) that Hypericum and hypericin have delayed effects on HPA axis control centers similar to those of imipramine; and (2) that select stress-induced changes in gene transcription in particular brain areas can be prevented by long-term treatment with either the prototypic tricyclic antidepressant imipramine or the herbiceutical St John's wort. However, imipramine appears to be more effective in blocking stress effects on the HPA axis than the plant extract.

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References

  1. Wheatly D . Hypericum extract—potential in the treatment of depression CNS Drugs 1998 9: 431–440

    Article  Google Scholar 

  2. Philipp M, Kohnen R, Hiller KO . Hypericum extract versus imipramine or placebo in patients with moderate depression: randomised multicentre study of treatment for eight weeks Br Med J 1999 319: 1534–1538

    Article  CAS  Google Scholar 

  3. Butterweck V, Wall A, Lieflander-Wulf U, Winterhoff H, Nahrstedt A . Effects of the total extract and fractions of Hypericum perforatum in animal assays for antidepressant activity Pharmacopsychiatry 1997 30 Suppl 2: 117–124

    Article  CAS  PubMed  Google Scholar 

  4. Winterhoff H, Butterweck V, Nahrstedt A, Gumbinger H, Schulz V, Erping S et al Pharmakologische Untersuchungen zur antidepressiven Wirkung von Hypericum perforatum L. In: Loew D, Rietbrock N (eds) Phytopharmaka in Forschung und klinischer Anwendung Steinkopff Verlag: Darmstadt 1995 39–56

    Chapter  Google Scholar 

  5. Müller WE, Rolli M, Schäfer C, Hafner U . Effects of hypericum extract (LI 160) in biochemical models of antidepressant activity Pharmacopsychiatry 1997 30 Suppl 2: 102–107

    Article  PubMed  Google Scholar 

  6. Simmen U, Burkard W, Berger K, Schaffner W, Lundstrom K . Extracts and constituents of Hypericum perforatum inhibit the binding of various ligands to recombinant receptors expressed with the Semliki Forest virus system J Recept Signal Transduct Res 1999 19: 59–74

    Article  CAS  PubMed  Google Scholar 

  7. Nahrstedt A, Butterweck V . Biologically active and other chemical constituents of the herb of Hypericum perforatum L Pharmacopsychiatry 1997 30 Suppl 2: 129–134

    Article  CAS  PubMed  Google Scholar 

  8. Chatterjee SS, Bhattacharya SK, Wonnemann M, Singer A, Muller WE . Hyperforin as a possible antidepressant component of hypericum extracts Life Sci 1998 63: 499–510

    Article  CAS  PubMed  Google Scholar 

  9. Singer A, Wonnemann M, Müller WE . Hyperforin, a major antidepressant constituent of St John's Wort, inhibits serotonin uptake by elevating free intracellular Na+ J Pharmacol Exp Ther 1999 290: 1363–1368

    CAS  PubMed  Google Scholar 

  10. Butterweck V, Petereit F, Winterhoff H, Nahrstedt A . Solubilized hypericin and pseudohypericin from Hypericum perforatum exert antidepressant activity in the forced swimming test Planta Medica 1998 64: 291–294

    Article  CAS  PubMed  Google Scholar 

  11. Butterweck V, Jürgenliemk G, Nahrstedt A, Winterhoff H . Flavonoids from Hypericum perforatum show antidepressant activity in the forced swimming test Planta Med 2000 66: 3–6

    Article  CAS  PubMed  Google Scholar 

  12. Calapai G, Crupi A, Firenzuoli F, Costantino G, Inferrera G, Campo GM et al. Effects of Hypericum perforatum on levels of 5-hydroxytryptamine, noradrenaline and dopamine in the cortex, diencephalon and brainstem of the rat J Pharm Pharmacol 1999 51: 723–728

    Article  CAS  PubMed  Google Scholar 

  13. Butterweck V, Nahrstedt A, Evans J, Rauser L, Savafe J, Popadak B et al. In vitro receptor screening of pure constituents of St John's wort reveals novel interactions with a number of GPCR's Soc Neurosci Abs 2001 27: (in press)

    Google Scholar 

  14. Butterweck V, Korte B, Winterhoff H . Pharmacological and endocrine effects of Hypericum perforatum and hypericin after repeated treatment Pharmacospsychiatry 2001 (in press)

  15. Brady LS, Whitfield H, Jr, Fox RJ, Gold PW, 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Brady LS, Gold PW, Herkenham M, Lynn AB, Whitfield H 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

    Article  CAS  PubMed  Google Scholar 

  17. Petty F . Plasma concentrations of gamma-aminobutyric acid (GABA) and mood disorders: a blood test for manic depressive disease? Clin Chem 1994 40: 296–302

    CAS  PubMed  Google Scholar 

  18. Plaznik A, Palejko W, Stefanski R, Kostowski W . Open field behavior of rats reared in different social conditions: the effects of stress and imipramine Pol J Pharmacol 1993 45: 243–252

    CAS  PubMed  Google Scholar 

  19. Lloyd KG, Zivkovic B, Scatton B, Morselli PL, Bartholini G . The gabaergic hypothesis of depression Prog Neuropsychopharmacol Biol Psychiatry 1989 13: 341–351

    Article  CAS  PubMed  Google Scholar 

  20. Breslow MF, Fankhauser MP, Potter RL, Meredith KE, Misiaszek J, Hope DG Jr . Role of gamma-aminobutyric acid in antipanic drug efficacy Am J Psychiatry 1989 146: 353–356

    Article  CAS  PubMed  Google Scholar 

  21. Holsboer F, Barden N . Antidepressants and hypothalamic-pituitary-adrenocortical regulation Endocr Rev 1996 17: 187–205

    Article  CAS  PubMed  Google Scholar 

  22. Barden N, Reul JM, Holsboer F . Do antidepressants stabilize mood through actions on the hypothalamic-pituitary-adrenocortical system? Trends Neurosci 1995 18: 6–11

    Article  CAS  PubMed  Google Scholar 

  23. Heuser I, Bissette G, Dettling M, Schweiger U, Gotthardt U, Schmider J et al. Cerebrospinal fluid concentrations of corticotropin-releasing hormone, vasopressin, and somatostatin in depressed patients and healthy controls: response to amitriptyline treatment Depress Anxiety 1998 8: 71–79

    Article  CAS  PubMed  Google Scholar 

  24. Mamalaki E, Kvetnansky R, Brady LS, Gold PW, Herkenham M . Repeated immobilization stress alters tyrosine hydroxylase, corticotropin-releasing hormone, and corticosteroid receptor mRNA levels in rat brain J Neuroendocrinol 1992 4: 689–699

    Article  CAS  PubMed  Google Scholar 

  25. Herman JP, Adams D, Prewitt C . Regulatory changes in neuroendocrine stress—integrative circuitry produced by a variable stress paradigm Neuroendocrinology 1995 61: 180–190

    Article  CAS  PubMed  Google Scholar 

  26. Sawchenko PE, Arias CA, Mortrud MT . Local tetrodotoxin blocks chronic stress effects on corticotropin-releasing factor and vasopressin messenger ribonucleic acids in hypophysiotropic neurons J Neuroendocrinol 1993 5: 341–348

    Article  CAS  PubMed  Google Scholar 

  27. Watanabe Y, McKittrick CR, Blanchard DC, Blanchard RJ, McEwen BS, Sakai RR . Effects of chronic social stress on tyrosine hydroxylase mRNA and protein levels Brain Res Mol Brain Res 1995 32: 176–180

    Article  CAS  PubMed  Google Scholar 

  28. Bowers G, Cullinan WE, Herman JP . Region-specific regulation of glutamic acid decarboxylase (GAD) mRNA expression in central stress circuits J Neurosci 1998 18: 5938–5947

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Lopez JF, Chalmers DT, Little KY, Watson SJ . Regulation of serotonin1A, glucocorticoid, and mineralocorticoid receptor in rat and human hippocampus: implications for the neurobiology of depression Biol Psychiatry 1998 43: 547–573

    Article  CAS  PubMed  Google Scholar 

  30. Wolfensohn S, Lloyd M . Handbook of Laboratory Animal Management and Welfare Oxford University Press: Oxford 1994

    Google Scholar 

  31. Kvetnansky R, Sun CL, Lake CR, Thoa N, Torda T, Kopin IJ . Effect of handing and forced immobilization on rat plasma levels of epinephrine, norepinephrine, and dopamine-β-hydroxylase Endocrinology 1978 103: 1868–1874

    Article  CAS  PubMed  Google Scholar 

  32. Paxinos G, Watson C . The Rat Brain in Stereotaxic Coordinates, 4th edn Academic Press: San Diego 1998

    Google Scholar 

  33. Isackson PJ, Huntsman MM, Murray KD, Gall CM . BDNF mRNA expression is increased in adult rat forebrain after limbic seizures: temporal patterns of induction distinct from NGF Neuron 1991 6: 937–948

    Article  CAS  PubMed  Google Scholar 

  34. Jensen JB, Jessop DS, Harbuz MS, Mork A, Sanchez C, Mikkelsen JD . Acute and long-term treatments with the selective serotonin reputake inhibitor citalopram modulate the HPA axis activity at different levels in male rats J Neuroendocrinol 1999 11: 465–471

    Article  CAS  PubMed  Google Scholar 

  35. Meltzer HY . Role of serotonin in depression Ann N Y Acad Sci 1990 600: 486–499

    Article  CAS  PubMed  Google Scholar 

  36. Welner SA, De Montigny C, Desroches J, Desjardins P, Suranyi-Cadotte BE . Autoradiographic quantification of serotonin1A receptors in rat brain following antidepressant drug treatment Synapse 1989 4: 347–352

    Article  CAS  PubMed  Google Scholar 

  37. Hall MD, el Mestikawy S, Emerit MB, Pichat L, Hamon M, Gozlan H . [3H]8-hydroxy-2-(di-n -propylamino)tetralin binding to pre- and postsynaptic 5-hydroxytryptamine sites in various regions of the rat brain J Neurochem 1985 44: 1685–1696

    Article  CAS  PubMed  Google Scholar 

  38. Marcinkiewicz M, Verge D, Gozlan H, Pichat L, Hamon M . Autoradiographic evidence for the heterogeneity of 5-HT1 sites in the rat brain Brain Res 1984 291: 159–163

    Article  CAS  PubMed  Google Scholar 

  39. Stockmeier CA, Dilley GE, Shapiro LA, Overholser JC, Thompson PA, Meltzer HY . Serotonin receptors in suicide victims with major depression Neuropsychopharmacology 1997 16: 162–173

    Article  CAS  PubMed  Google Scholar 

  40. Arango V, Underwood MD, Gubbi AV, Mann JJ . Localized alterations in pre- and postsynaptic serotonin binding sites in the ventrolateral prefrontal cortex of suicide victims Brain Res 1995 688: 121–133

    Article  CAS  PubMed  Google Scholar 

  41. Mizuta T, Segawa T . Chronic effects of imipramine and lithium on 5-HT receptor subtypes in rat frontal cortex, hippocampus and choroid plexus: quantitative receptor autoradiographic analysis Jpn J Pharmacol 1989 50: 315–326

    Article  CAS  PubMed  Google Scholar 

  42. Subhash MN, Srinivas BN, Vinod KY, Jagadeesh S . Modulation of 5-HT1A receptor mediated response by fluoxetine in rat brain J Neural Transm 2000 107: 377–387

    Article  CAS  PubMed  Google Scholar 

  43. Newman ME, Gur E, Dremencov E, Garcia F, Lerer B, Van de Kar LD . Chronic clomipramine alters presynaptic 5-HT(1B) and postsynaptic 5-HT(1A) receptor sensitivity in rat hypothalamus and hippocampus, respectively Neuropharmacology 2000 39: 2309–2317

    Article  CAS  PubMed  Google Scholar 

  44. Yoshioka M, Matsumoto M, Numazawa R, Togashi H, Smith CB, Saito H . Changes in the regulation of 5-hydroxytryptamine release by alpha2-adrenoceptors in the rat hippocampus after long-term desipramine treatment Eur J Pharmacol 1995 294: 565–570

    Article  CAS  PubMed  Google Scholar 

  45. Nestler EJ, McMahon A, Sabban EL, Tallman JF, Duman RS . Chronic antidepressant administration decreases the expression of tyrosine hydroxylase in the rat locus coeruleus Proc Natl Acad Sci USA 1990 87: 7522–7526

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Herman JP, Cullinan WE . Neurocircuitry of stress: central control of the hypothalamo-pituitary-adrenocortical axis Trends Neurosci 1997 20: 78–84

    Article  CAS  PubMed  Google Scholar 

  47. Harbuz MS, Lightman SL . Responses of hypothalamic and pituitary mRNA to physical and psychological stress in the rat J Endocrinol 1989 122: 705–711

    Article  CAS  PubMed  Google Scholar 

  48. Harbuz MS, Jessop DS, Lightman SL, Chowdrey HS . The effects of restraint or hypertonic saline stress on corticotrophin-releasing factor, arginine vasopressin, and proenkephalin A mRNAs in the CFY, Sprague–Dawley and Wistar strains of rat Brain Res 1994 667: 6–12

    Article  CAS  PubMed  Google Scholar 

  49. Kalin NH, Takahashi LK, Chen FL . Restraint stress increases corticotropin-releasing hormone mRNA content in the amygdala and paraventricular nucleus Brain Res 1994 656: 182–186

    Article  CAS  PubMed  Google Scholar 

  50. Makino S, Smith MA, Gold PW . Increased expression of corticotropin-releasing hormone and vasopressin messenger ribonucleic acid (mRNA) in the hypothalamic paraventricular nucleus during repeated stress: association with reduction in glucocorticoid receptor mRNA levels Endocrinology 1995 136: 3299–3309

    Article  CAS  PubMed  Google Scholar 

  51. Bartanusz V, Aubry JM, Jezova D, Baffi J, Kiss JZ . Up-regulation of vasopressin mRNA in paraventricular hypophysiotrophic neurons after acute immobilization stress Neuroendocrinology 1993 58: 625–629

    Article  CAS  PubMed  Google Scholar 

  52. Herman JP . In situ hybridization analysis of vasopressin gene transcription in the paraventricular and supraoptic nuclei of the rat: regulation by stress and glucocorticoids J Comp Neurol 1995 363: 15–27

    Article  CAS  PubMed  Google Scholar 

  53. Lightman SL, Young WSI . Corticotrophin-releasing factor, vasopressin and proopiomelanocortin mRNA responses to stress and opiates in the rat J Physiol (Lond) 1988 403: 511–523

    Article  CAS  Google Scholar 

  54. Darlington DN, Barraclough CA, Gann DS . Hypotensive hemorrhage elevates corticotropin-releasing hormone messenger ribonucleic acid (mRNA) but not vasopressin mRNA in the rat hypothalamus Endocrinology 1992 130: 1281–1288

    CAS  PubMed  Google Scholar 

  55. Herman JP, Wiegand SJ, Watson SJ . Regulation of basal corticotropin-releasing hormone and arginine vasopressin messenger ribonucleic acid expression in the paraventricular nucleus: effects of selective hypothalamic deafferentations Endocrinology 1990 127: 2408–2417

    Article  CAS  PubMed  Google Scholar 

  56. Schmidt ED, Janszen AW, Binnekade R, Tilders FJ . Transient suppression of resting corticosterone levels induces sustained increase of AVP stores in hypothalamic CRH-neurons of rats J Neuroendocrinol 1997 9: 69–77

    Article  CAS  PubMed  Google Scholar 

  57. Ma XM, Lightman SL . The arginine vasopressin and corticotrophin-releasing hormone gene transcription responses to varied frequencies of repeated stress in rats J Physiol (Lond) 1998 510: 605–614

    Article  CAS  Google Scholar 

  58. Johnson MR, Lydiard RB, Ballenger JC . Panic disorder. Pathophysiology and drug treatment Drugs 1995 49: 328–344

    Article  CAS  PubMed  Google Scholar 

  59. Stewart JW, McGrath PJ, Quitkin FM, Rabkin JG, Harrison W, Wager S et al. Chronic depression: response to placebo, imipramine, and phenelzine J Clin Psychopharmacol 1993 13: 391–396

    CAS  PubMed  Google Scholar 

  60. Korf J, Venema K . Desmethylimipramine enhances the release of endogenous GABA and other neurotransmitter amino acids from the rat thalamus J Neurochem 1983 40: 946–950

    Article  CAS  PubMed  Google Scholar 

  61. Sawchenko PE, Swanson LW . The organization of forebrain afferents to the paraventricular and supraoptic nuclei of the rat J Comp Neurol 1983 218: 121–144

    Article  CAS  PubMed  Google Scholar 

  62. Lai CT, Tanay VA, Charrois GJ, Baker GB, Bateson AN . Effects of phenelzine and imipramine on the steady-state levels of mRNAs that encode glutamic acid decarboxylase (GAD67 and GAD65), the GABA transporter GAT-1 and GABA transaminase in rat cortex Naunyn Schmiedebergs Arch Pharmacol 1998 357: 32–38

    Article  CAS  PubMed  Google Scholar 

  63. Delbende C, Delarue C, Lefebvre H, Bunel DT, Szafarczyk A, Mocaer E et al. Glucocorticoids, transmitters and stress Br J Psychiatry 1992 Suppl 15: 24–35

    Article  Google Scholar 

  64. Watanabe Y, Sakai RR, McEwen BS, Mendelson S . Stress and antidepressant effects on hippocampal and cortical 5-HT1A and 5-HT2 receptors and transport sites for serotonin Brain Res 1993 615: 87–94

    Article  CAS  PubMed  Google Scholar 

  65. Meijer OC, Van Oosten RV, De Kloet ER . Elevated basal troughlevels of corticosterone suppress hippocampal 5-hydroxy-tryptamine(1A) receptor expression in adrenally intact rats:implication for the pathogenesis of depression Neuroscience 1997 80: 419–426

    Article  CAS  PubMed  Google Scholar 

  66. Drevets WC, Frank E, Price JC, Kupfer DJ, Holt D, Greer PJ et al. PET imaging of serotonin 1A receptor binding in depression Biol Psychiatry 1999 46: 1375–1387

    Article  CAS  PubMed  Google Scholar 

  67. Sargent PA, Kjaer KH, Bench CJ, Rabiner EA, Messa C, Meyer J et al. Brain serotonin1A receptor binding measured by position emission tomography with [11C]WAY-100635: effects of depression and antidepressant treatment Arch Gen Psychiatry 2000 57: 174–180

    Article  CAS  PubMed  Google Scholar 

  68. Jacobs BL, Praag H, Gage FH . Adult brain neurogenesis and psychiatry: a novel theory of depression Mol Psychiatry 2000 5: 262–269

    Article  CAS  PubMed  Google Scholar 

  69. Lindsay RM, Wiegand SJ, Altar CA, DiStefano PS . Neurotrophic factors: from molecule to man Trends Neurosci 1994 17: 182–190

    Article  CAS  PubMed  Google Scholar 

  70. Herman JP, Schafer MK, Young EA, Thompson R, Douglass J, Akil H et al. Evidence for hippocampal regulation of neuroendocrine neurons of the hypothalamo-pituitary-adrenocortical axis J Neurosci 1989 9: 3072–3082

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Young EA, Haskett RF, Murphy-Weinberg V, Watson SJ, Akil H . Loss of glucocorticoid fast feedback in depression Arch Gen Psychiatry 1991 48: 693–699

    Article  CAS  PubMed  Google Scholar 

  72. Nibuya M, Morinobu S, Duman RS . Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments J Neurosci 1995 15: 7539–7547

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Tao X, Finkbeiner S, Arnold DB, Shaywitz AJ, Greenberg ME . Ca2+ influx regulates BDNF transcription by a CREB family transcription factor-dependent mechanism Neuron 1998 20: 709–726

    Article  CAS  PubMed  Google Scholar 

  74. Nibuya M, Nestler EJ, Duman RS . Chronic antidepressant administration increases the expression of cAMP response element binding protein (CREB) in rat hippocampus J Neurosci 1996 16: 2365–2372

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Smith MA, Makino S, Kvetnansky R, Post RM . Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus J Neurosci 1995 15: 1768–1777

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Kuroda Y, McEwen BS . Effect of chronic restraint stress and tianeptine on growth factors, growth-associated protein-43 and microtubule-associated protein 2 mRNA expression in the rat hippocampus Brain Res Mol Brain Res 1998 59: 35–39

    Article  CAS  PubMed  Google Scholar 

  77. Brady LS . Stress, antidepressant drugs, and the locus coeruleus Brain Res Bull 1994 35: 545–556

    Article  CAS  PubMed  Google Scholar 

  78. Melia KR, Nestler EJ, Duman RS . Chronic imipramine treatment normalizes levels of tyrosine hydroxylase in the locus coeruleus of chronically stressed rats Psychopharmacology 1992 108: 23–26

    Article  CAS  PubMed  Google Scholar 

  79. Calogero AE, Gallucci WT, Chrousos GP, Gold PW . Catecholamine effects upon rat hypothalamic corticotropin-releasing hormone secretion in vitro J Clin Invest 1988 82: 839–846

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Funding was supplied by the NIMH Intramural Research Program and by Lichtwer Pharma (for VB).

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  1. Institute of Pharmacology and Toxicology, Domagkstrasse 12, Muenster, 48149, Germany

    V Butterweck & H Winterhoff

  2. Section on Functional Neuroanatomy, National Institute of Mental Health, Bethesda, 20892, Maryland, USA

    V Butterweck & M Herkenham

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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 6, 547–564 (2001). https://doi.org/10.1038/sj.mp.4000937

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