Advertisement
Research Article| Volume 28, ISSUE 7, P620-628, October 01, 1990

5-HT1A receptor responsivity in unipolar depression Evaluation of ipsapirone-induced ACTH and cortisol secretion in patients and controls

DOI:https://doi.org/10.1016/0006-3223(90)90400-V
5-HT1A receptor responsivity in unipolar depression Evaluation of ipsapirone-induced ACTH and cortisol secretion in patients and controls
Previous ArticleChronic lithium treatment prevents atropine-induced supersensitivity of the muscarinic phosphoinositide response in rat hippocampus
Next ArticleElevated CSF protein in male patients with depression
      This paper is only available as a PDF. To read, Please Download here.

      Abstract

      The selective 5-HT1A receptor ligand ipsapirone (IPS) induces corticotropin (ACTH) and cortisol secretion in humans. To explore 5-HT1A receptor-mediated hypothalamic-pituitary-adrenal (HPA) system activation in depression, 24 subjects (12 patients with unipolar depression and 12 individually matched controls) were given 0.3 mg/kg IPS or placebo in random order. Compared with controls, the depressed patients exhibited significantly decreased ACTH and cortisol responses to IPS in association with increased basal cortisol secretion. The impaired HPA response following 5-HT1A receptor challenge in unipolar depression could have resulted from glucocorticoid-dependent subsensitivity of the (post-synaptic) 5-HT1A receptor itself and/or from a defective postreceptor signaling pathway [inhibitory guanine nucleotide-binding protein (Gi)-adenylate cyclase complex function], thus supporting the hypothesis that a disintegrated 5-HT and HPA system interaction may be present in depression. Future studies of the HPA response to direct-acting 5-HT1A ligands, such as IPS, should facilitate the assessment of 5-HT/HPA system integrity in various affective disorders and its involvement in psychotropic drug effects.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Register: Create an account
      Institutional Access: Sign in to ScienceDirect

      References

        • Bagdy G.
        • Calogero A.E.
        • Aulakh C.S.
        • Szemeredi K.
        • Murphy D.L.
        Long-term cortisol treatment impairs behavioral and neuroendocrine responses to 5-HT1 agonists in the rat.
        Neuroendocrinology. 1989; 50: 241-247
        • Cowen P.J.
        Psychotropic drugs and human 5-HT neuroendocrinology.
        Trends Pharmacol Sci. 1987; 8: 105-108
        • De Kloet E.R.
        • Sybesma H.
        • Reul H.
        Selective control by corticosterone of serotonin1 receptor capacity in raphe-hippocampal system.
        Neuroendocrinology. 1986; 42: 513-522
        • De Souza E.B.
        Serotonin and dopamine receptors in the rat pituitary gland: Autoradiographic identification, characterization, and localization.
        Endocrinology. 1986; 119: 1534-1542
        • Feldman S.
        • Conforti N.
        • Melamed E.
        Paraventricular nucleus serotonin mediates neurally stimulated adrenocortical secretion.
        Brain Res Bull. 1987; 18: 165-170
        • Furman B.L.
        • Waton N.G.
        5-Hydroxytryptamine and peripheral secretory mechanisms.
        in: Fozard J.R. The Peripheral Actions of 5-Hydroxytryptamine. Oxford University Press, Oxford1989: 282
        • Gibbs D.M.
        • Vale W.
        Effect of the serotonin reuptake inhibitor fluoxetine on corticotropin-releasing factor and vasopressin secretion into hypophysial portal blood.
        Brain Res. 1983; 280: 176-179
        • Gilbert F.
        • Brazell C.
        • Tricklebank M.S.
        • Stahl S.M.
        Activation of the 5-HT1A receptor subtype increases rat plasma ACTH concentrations.
        Eur J Pharmacol. 1988; 147: 431-437
        • Gold P.W.
        • Chrousos G.
        • Kellner C.
        • et al.
        Psychiatric implications of basic and clinical studies with corticotropin-releasing factor.
        Am J Psychiatry. 1984; 141: 619-627
        • Gustafsson J.A.
        • Carlstedt-Duke J.
        • Poellinger L.
        • et al.
        Biochemistry, molecular biology, and physiology of the glucocorticoid receptor.
        Endocr Rev. 1987; 8: 185-234
        • Haleem D.J.
        • Kennett G.A.
        • Whitton P.S.
        • Curzon G.
        8-OH-DPAT increases corticosterone but not other 5-HT1A receptor-dependent responses more in females.
        Eur J Pharmacol. 1989; 164: 435-443
        • Holsboer F.
        Implications of altered limbic-hypothalamic-pituitary-adrenocortical (LHPA) function for neurobiology of depression.
        Acta Psychiatr Scand. 1988; 78: 72-111
        • Holsboer F.
        • Bardeleben U.
        • Gerken A.
        • Stalla G.
        • Müller O.
        Blunted corticotropin and normal cortisol responses to human corticotropin-releasing factor in depression.
        N Engl J Med. 1984; 311: 1127
        • Koenig J.I.
        • Gudelsky G.A.
        • Meltzer H.Y.
        Stimulation of corticosterone and β-endorphin secretion in the rat by selective 5-HT receptor subtype activation.
        Eur J Pharmacol. 1987; 137: 1-8
        • Koenig J.I.
        • Meltzer H.Y.
        • Gudelsky G.A.
        5-Hydroxytryptamine1A receptor-mediated effects of buspirone, gepirone and ipsapirone.
        Pharmacol Biochem Behav. 1988; 29: 711-715
        • Lesch K.P.
        • Beckmann H.
        On the serotonin hypothesis of depression.
        Fortschr Neurol Psychiatr. 1990; (in press)
        • Lesch K.P.
        • Laux G.
        • Schulte H.M.
        • Pfüller H.
        • Beckmann H.
        Corticotropin and cortisol response to human CRH as a probe for HPA system integrity in major depressive disorder.
        Psychiatry Res. 1988; 24: 25-34
        • Lesch K.P.
        • Rupprecht R.
        • Poten B.
        • et al.
        Endocrine responses to 5-hydroxytryptamine-1A receptor activation by ipsapirone in humans.
        Biol Psychiatry. 1989; 26: 203-205
        • Lesch K.P.
        • Söhnle K.
        • Poten B.
        • Rupprecht R.
        • Schulte H.M.
        Corticotropin and cortisol secretion following central 5-hydroxytryptamine-1A (5-HT1A) receptor activation: Effects of 5-HT receptor and β-adrenoceptor antagonists.
        J Clin Endocrinol Metab. 1990; 70: 670-674
        • Liposits Z.
        • Phelix C.
        • Paull W.K.
        Synaptic interaction of serotonergic axons and corticotropin releasing factor (CRF) synthesizing neurons in the hypothalamic paraventricular nucleus of the rat.
        Histochemistry. 1987; 86: 541-549
        • Lorens S.A.
        • Van de Kar L.D.
        Differential effects of serotonin (5-HT1A and 5-HT2) agonists and antagonists on renin and corticosterone secretion.
        Neuroendocrinology. 1987; 45: 305-310
        • Lowy M.T.
        • Meltzer H.Y.
        Stimulation of serum cortisol and prolactin secretion in humans by MK-212, a centrally active serotonin agonist.
        Biol Psychiatry. 1988; 23: 818-828
        • Meltzer H.Y.
        • Lowy M.T.
        The serotonin hypothesis of depression.
        in: Meltzer H.Y. Psychopharmacology: The Third Generation of Progress. Raven, New York1987: 513-526
        • Meltzer H.V.
        • Umberköman-Wiita B.
        • Robertson A.
        • Tricou B.J.
        • Lowy M.
        • Perline R.
        Effect of 5-hydroxytryptophan on serum cortisol levels in major affective disorder. I. Enhanced response in depression and mania.
        Arch Gen Psychiatry. 1984; 41: 366-374
        • Murphy D.L.
        • Mueller E.A.
        • Garrick N.A.
        • Aulakh C.S.
        Use of serotonergic agents in the clinical assessment of central serotonin function.
        J Clin Psychiatry. 1986; 47: 9-15
        • Murphy D.L.
        • Mueller E.A.
        • Hill J.L.
        • Tolliver T.J.
        • Jacobsen F.M.
        Comparative anxiogenic, neuroendocrine, and other physiologic effects of m-chlorophenylpiperazine given intravenously or orally to healthy volunteers.
        Psychopharmacology. 1989; 98: 275-282
        • Pazos A.
        • Hoyer D.
        • Dietl M.M.
        • Palacios J.M.
        Autoradiography of serotonin receptors.
        in: Osborne N.N. Hamon M. Neuronal Serotonin. Wiley, Chichester, England1988: 57-92
        • Peroutka S.J.
        5-Hydroxytryptamine receptor subtypes: Molecular, biochemical and physiological characterization.
        Trends Neurosci. 1988; 11: 496-500
        • Saito N.
        • Guitart X.
        • Hayward M.
        • Tallman J.F.
        • Duman R.S.
        • Nestler E.J.
        Corticosterone differentially regulates the expression of Gsα and Giα messenger RNA and protenin in rat cerebral cortex.
        in: Proc Natl Acad Sci USA. 86. 1989: 3906-3910
        • Sawchenko P.E.
        • Swanson L.W.
        • Steinbusch H.W.M.
        • Verhofstad A.A.J.
        The distribution and cells of origin of serotonergic inputs to the paraventricular and supraoptic nuclei of the rat.
        Brain Res. 1983; 277: 355-360
        • Schulte H.M.
        • Chrousos G.
        • Avgerinos P.
        • et al.
        The corticotropin-releasing hormone stimulation test: A possible aid in the evaluation of patients with adrenal insufficiency.
        J Clin Endocrinol Metab. 1984; 58: 1064-1069
        • Spitzer R.L.
        • Endicott J.
        • Robins E.
        Research Diagnostic Criteria (RDC) for a Selected Group of Functional Disorders.
        3rd ed. New York State Psychiatric Institute, New York1978
        • Traber J.
        • Glaser T.
        5-HT1A receptor-related anxiolytics.
        Trends Pharmacol Sci. 1987; 8: 432-437
        • Tuomisto J.
        • Männistö P.
        Neurotransmitter regulation of pituitary hormones.
        Pharmacol Rev. 1985; 37: 249-267
        • Van de Kar L.D.
        • Karteszi M.
        • Bethea C.L.
        • Ganong W.
        Serotonergic stimulation of prolactin and corticosterone secretion is mediated by different pathways from the mediobasal hypothalamus.
        Neuroendocrinology. 1985; 41: 380-384

      Article info

      Publication history

      Received in revised form: April 10, 1990
      Received: October 15, 1989

      Footnotes

      ☆Part of this work was presented at the VIII World Congress of Psychiatry, Athens, Greece, October 12–19, 1989.

      Identification

      DOI: https://doi.org/10.1016/0006-3223(90)90400-V

      Copyright

      © 1990 Published by Elsevier Inc.

      ScienceDirect

      Access this article on ScienceDirect
      We use cookies to help provide and enhance our service and tailor content. To update your cookie settings, please visit the for this site.
      Copyright © 2023 Elsevier Inc. except certain content provided by third parties. The content on this site is intended for healthcare professionals.


      RELX