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5-Hydroxytryptamine1A (5-HT1A) Receptor Responsivity in Anxiety Disorders and Depression

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New Concepts in Anxiety

Abstract

Based on radioligand binding studies, four pharmacologically distinct populations of 5-HT recognition sites located on neurons in the central nervous system have been designated 5-HT1, 5-HT2, 5-HT3 and 5-HT4. Moreover, current research indicates that 5-HT1 receptors comprise A, B, C, D and E subtypes (Glennon, 1990) and that the 5-HT2 receptor may be subdivided into two types (or possibly affinity states), while for the 5-HT3 binding site several subpopulations have been postulated, although no functional correlates such as second-messenger coupling, membrane effects and models for physiologic functions or behaviour have yet been identified for the 1E and 4 subtvpes.

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References

  • Bagdy, G., Calogero, A. E., Murphy, D. L. and Szemeredi, K. (1989). Serotonin agonists cause parallel activation of the sympathoadrenomedullary system and the hypothalamo-pituitary-adrenocortical axis in conscious rats. Endocrinology, 125, 2664–9.

    Article  CAS  PubMed  Google Scholar 

  • Calogero, A. E., Bagdy, G., Szemeredi, K., Tartaglia, M. E., Gold, P. W. and Chrousos, G. P. (1990). Mechanisms of serotonin receptor agonist-induced activation of the hypothalamic—pituitary—adrenal axis in the rat. Endocrinology, in press.

    Google Scholar 

  • Calogero, A. E., Bernadini, R., Margioris, A. N., Bagdy, G., Gallucci, W. T., Nunson, P. J., Tamarkin, L., Tomai, T. P., Brady, L., Gold, P. W. and Chrousos, G. P. (1989). Effects of serotonergic agonists and antagonists on corticotropin-releasing hormone secretion by explanted rat hypothalami. Peptides, 10, 189–96.

    Article  CAS  PubMed  Google Scholar 

  • De Kloet, E. R., Sybesma, H. and Reul, J. M. H. M. (1986). Selective control by corticosterone of serotonin 1 receptor capacity in raphe—hippocampus system. Neuroendocrinology, 42, 513–21.

    Article  CAS  PubMed  Google Scholar 

  • De Souza, E. B. (1986). Serotonin and dopamine receptors in the rat pituitary gland: autoradiographic identification, characterization, and localization. Endocrinology, 119, 1534–42.

    Article  PubMed  Google Scholar 

  • Feldman, S., Conforti, N. and Nelamed, E. (1987). Paraventricular nucleus serotonin mediates neurally stimulated adrenocortical secretion. Brain. Res. Bull., 18, 165–70.

    Article  CAS  PubMed  Google Scholar 

  • Furman, B. L. and Waton, N. G. (1989). 5-Hydroxytryptamine and peripheral secretory mechanisms. In Fozard, J. R. (ed.), The Peripheral Actions of 5-Hydroxytryptamine, Oxford University Press, Oxford, 274–300.

    Google Scholar 

  • Gibbs, D. M. and Vale, W. (1983). Effect of the serotonin reuptake inhibitor fluoxetine on corticotropin-releasing factor and vasopressin secretion into hypophysial portal blood. Brain Res., 280, 176–9.

    Article  CAS  PubMed  Google Scholar 

  • Gilbert, F., Brazell, C., Tricklebank, M. D. and Stahl, S. M. (1988). Activation of the 5-HT1A receptor subtype increases rat plasma ACTH concentrations. Eur. J. Pharmacol., 147, 431–7.

    Article  CAS  PubMed  Google Scholar 

  • Gilman, A. G. (1987). G proteins: transduction of receptor-generated signals. Ann. Rev. Biochem., 56, 615–49.

    Article  CAS  PubMed  Google Scholar 

  • Glennon, R. A. (1990). Serotonin receptors: clinical implications. Neurosci. Biobehav. Rev., 14, 35–47.

    Article  CAS  PubMed  Google Scholar 

  • Goodwin, G. M., De Souza, R. J., Green, A. R. and Heal, D. J. (1987). The pharmacology of the behavioural and hypothermic responses of rats to 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Psychopharmacology, 91, 506–11.

    Article  CAS  PubMed  Google Scholar 

  • Grahame-Smith, D. G. (1989). Neuropharmacological adaptive effects in the actions of antidepressant drugs, ECT and lithium. In Briley, M. and Fillion, G. (eds), New Concepts in Depression, Macmillan, London, 1–14.

    Google Scholar 

  • Green, A. R. and Goodwin, G. M. (1987). The pharmacology of the hypothermic response of rodents to 8-OH-DPAT administration and the effect of psychotropic drug administration on this response. In Dourish, C. T., Ahlenius, S. and Hutson, P. H. (eds), Brain 5-HT1A Receptors, Ellis Horwood, Chichester, 161–76.

    Google Scholar 

  • Gudelsky, G. A., Koenig, J. I. and Meltzer, H. Y. (1986). Thermoregulatory responses to serotonin (5-HT) receptor stimulation in the rat. Neuropharmacology, 25, 1307–13.

    Article  CAS  PubMed  Google Scholar 

  • Haleem, D. J., Kennett, G. A., Whitton, P. S. and Curzon, G. (1989). 8-OH-DPAT increases corticosterone but not other 5-HT1A receptor-dependent responses more in females. Eur. J. Pharmacol., 164, 435–43.

    Article  CAS  PubMed  Google Scholar 

  • Harfstrand, A., Fuxe, K., Cintra, A. and Agnati, L. F. (1986). Glucocorticosteroid receptor immunoreactivity in monoaminergic neurons of the rat brain. Proc. Natl Acad. Sci. USA, 83, 9779–83.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hartig, P. R. (1989). Molecular biology of 5-HT receptors. Trends Pharmacol. Sci., 10, 64–9.

    Article  CAS  PubMed  Google Scholar 

  • Heninger, G. R., Charney, D. S., Price, L. H., Delgado, P., Woods, S. and Goodman, U. (1989). Effects of serotonergic agonists on neuroendocrine responses of rhesus monkeys and patients with depression and anxiety disorders. In Dahl, S. G. and Gram, L. F. (eds), Clinical Pharmacology in Psychiatry, Springer, Berlin, 94–104.

    Chapter  Google Scholar 

  • Holsboer, F. (1989). Psychiatric implications of altered limbic—hypothalamic—pituitary—adrenocortical activity. Eur. Arch. Psychiat. Neurol. Sci., 238, 302–22.

    Article  CAS  Google Scholar 

  • Kennett, G. A., Marcou, M., Dourish, C. T. and Curzon, G. (1987). Single administration of 5-HT1A agonists decreases 5-HT1A presynaptic, but not postsynaptic receptor-mediated responses: relationship to antidepressant-like action. Eur. J. Pharmacol., 138, 53–60.

    Article  CAS  PubMed  Google Scholar 

  • King, B. H., Brazell, C., Dourish, C. T. and Middlemiss, D. N. (1989). Activation of the 5-HT2 receptor subtype increases rat plasma ACTH concentration. Br. J. Pharmacol., 98, 686P.

    Google Scholar 

  • Koenig, J. I., Gudelsky, G. A. and Meltzer, H. Y. (1987). Stimulation of corticosterone and β-endorphin secretion in the rat by selective 5-HT receptor subtype activation. Eur. J. Pharmacol., 137, 1–8.

    Article  CAS  PubMed  Google Scholar 

  • Lesch, K. P., Laux, G., Schulte, H. M., Pfuller, H. and Beckmann, H. (1988). Corticotropin and Cortisol response to human CRH as a probe for HPA system integrity in major depressive disorder. Psychiatry Res., 24, 25–34.

    Article  CAS  PubMed  Google Scholar 

  • Lesch, K. P., Mayer, S., Disselkamp-Tietze, J., Hoh, A., Schoellnhammer, G. and Schulte, H. M. (1990a). Subsensitivity of the 5-hydroxytryptamine1A (5-HT1A) receptor-mdiated hypothermic response to ipsapirone in unipolar depression. Life Sci., 46, 1271–7.

    Article  CAS  PubMed  Google Scholar 

  • Lesch, K. P., Mayer, S., Disselkamp-Tietze, J., Hoh, A., Wiesmann, M., Osterheider, M. and Schulte, H. M. (1991). 5-HT1A receptor responsivity in unipolar depression: evaluation of ipsapirone-induced ACTH and Cortisol secretion in patients and controls. Biol. Psychiatry, in press.

    Google Scholar 

  • Lesch, K. P., Mayer, S., Hoh, A., Disselkamp-Tietze, J., Rupprecht, R., Schmidtke, A., Osterheider, M. and Beckmann, H. (1989a). 5-Hydroxytryptamine-1A (5-HT1A) receptor function in affective disorders. Pharmacopsychiatry, 22, 205.

    Google Scholar 

  • Lesch, K. P., Rupprecht, R., Poten, B., Muller, U., Soehnle, K., Fritze, J. and Schulte, H. M. (1989b). Endocrine responses to 5-hydroxytryptamine-1A receptor activation by ipsapirone in humans. Biol. Psychiatry., 26, 203–5.

    Article  CAS  PubMed  Google Scholar 

  • Lesch, K. P., Rupprecht, R., Poten, B., Sohnle, K. and Schulte, H. M. (1990b). The pharmacology of the hypothermic response to 5-HT1A receptor activation in humans. Eur. J. Clin. Pharmacol., 39, 13–17.

    Article  Google Scholar 

  • Lesch, K. P., Sohnle, K., Poten, B., Rupprecht, R., Schoellnhammer, G. and Schulte, H. M. (1990c). 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., 70, 670–4.

    Article  CAS  PubMed  Google Scholar 

  • Liposits, Z., Phelix, C. and Pauli, W. K. (1987). Synaptic interaction of serotonergic axons and corticotropin releasing factor (CRF) synthesizing neurons in the hypothalamic paraventricular nucleus of the rat. Histochemistry, 86, 541–9.

    Article  CAS  PubMed  Google Scholar 

  • Lorens, S. A. and Van de Kar, L. D. (1987). Differential effects of serotonin (5-HT1A and 5-HT2) agonists and antagonists on renin and corticosterone secretion. Neuroendocrinology, 45, 305–10.

    Article  CAS  PubMed  Google Scholar 

  • Lowy, M. T. and Meltzer, H. Y. (1988). Stimulation of serum Cortisol and prolactin secretion in humans by MK-212, a centrally active serotonin agonist. Biol. Psychiatry, 23, 818–28.

    Article  CAS  PubMed  Google Scholar 

  • Meltzer, H. Y. and Nash, J. F. (1988). Serotonin and mood: neuroendocrine aspects. In Ganten, F., Pfaff, D. and Fuxe, F. (eds), Current Topics in Neuroendocrinology, Springer, Berlin, 183–210.

    Google Scholar 

  • Michell, R. H. (1989). Post-receptor signalling pathways. Lancet, i, 765–8.

    Article  Google Scholar 

  • Moriarty, T. M., Padrell, E., Carty, D. J., Omri, G., Landau, E. M. and Iyengar, R. (1990). Go protein as signal transducer in the pertussis toxin-sensitive phosphatidylinositol pathway. Nature, 343, 79–82.

    Article  CAS  PubMed  Google Scholar 

  • Murphy, D. L., Mueller, E. A., Garrick, N. A. and Aulakh, C. S. (1986). Use of serotonergic agents in the clinical assessment of central serotonin function. J. Clin. Psychiatry, 47, 9–15.

    CAS  PubMed  Google Scholar 

  • Murphy, D. L., Zohar, J., Benkelfat, C., Pato, M. T., Pigott, T. A. and Insel, T. R. (1989). Obsessive—compulsive disorder as a 5-HT subsystem-related behavioural disorder. Brit. J. Psychiatry, 155 (suppl. 8), 15–24.

    Article  Google Scholar 

  • Newman, M. E. and Lerer, B. (1988). Chronic electroconvulsive shock and desipramine reduce the degree of inhibition by 5-HT and carbachol of forskolin-stimulated adenylate cyclase in rat hippocampal membranes. Eur. J. Pharmacol., 148, 257–64.

    Article  CAS  PubMed  Google Scholar 

  • Pazos, A., Hoyer, D., Dietl, M. M. and Palacios, J. M. (1988). Autoradiography of serotonin receptors. In Osborne, N. N. and Hamon, M. (eds), Neuronal Serotonin, Wiley, Chichester, 57–92.

    Google Scholar 

  • Saito, N., Guitart, X., Hayward, M., Tallman, J. F., Duman, R. S. and Nestler, E.J. (1989). Corticosterone differentially regulates the expression of Gsα and Giα messenger RNA and protein in rat cerebral cortex. Proc. Natl Acad. Sci. USA, 86, 3906–10.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sapolsky, R. M., Krey, L. C. and McEwan, B. S. (1986). The neuroendocrinology of stress and aging: the glucorticoid cascade hypothesis. Endocr. Rev., 7, 284–312.

    Article  CAS  PubMed  Google Scholar 

  • Sternweis, P. C. and Pang, I. H. (1990). The G protein-channel connection. Trends Neurosci., 13, 122–6.

    Article  CAS  PubMed  Google Scholar 

  • Traber, J. and Glaser, T. (1987). 5-HT1A receptor-related anxiolytics. Trends Pharmacol Sci., 8, 432–7.

    Article  CAS  Google Scholar 

  • Van de Kar, S. D. (1989). Neuroendocrine aspects of the serotonergic hypothesis of depression. Neurosci. Biobehav. Rev., 13, 237–46.

    Article  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Laboratory of Clinical Sciences, NIMH, NIH Clinical Center, 10/3D41, 9000 Rockville Pike, Bethesda, MA, 20892, USA

    K. P. Lesch

Authors
  1. K. P. Lesch
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  2. M. Osterheider
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Editor information

Editors and Affiliations

  1. Pierre Fabre Médicament, Castres, France

    M. Briley

  2. Psychopharmacology Research Unit, UMDS, Guy’s Hospital, London, SE1 9RT, UK

    S. E. File

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© 1991 Macmillan Publishers Limited

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Lesch, K.P., Osterheider, M. (1991). 5-Hydroxytryptamine1A (5-HT1A) Receptor Responsivity in Anxiety Disorders and Depression. In: Briley, M., File, S.E. (eds) New Concepts in Anxiety. Palgrave, London. https://doi.org/10.1007/978-1-349-11847-2_8

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  • DOI: https://doi.org/10.1007/978-1-349-11847-2_8

  • Publisher Name: Palgrave, London

  • Print ISBN: 978-1-349-11849-6

  • Online ISBN: 978-1-349-11847-2

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