Hostname: page-component-78c5997874-v9fdk Total loading time: 0 Render date: 2024-11-17T07:25:16.028Z Has data issue: false hasContentIssue false
  • English
  • Français

5-HT1A Receptor Sensitivity in Major Depression

A Neuroendocrine Study with Buspirone

Published online by Cambridge University Press:  02 January 2018

P. J. Cowen ,
A. C. Power ,
C. J. Ware  and
I. M. Anderson
P. J. Cowen*
Affiliation:
Psychopharmacology Research Unit, Littlemore Hospital, Oxford OX4 4XN
A. C. Power
Affiliation:
Warneford Hospital, Oxford
C. J. Ware
Affiliation:
Warneford Hospital, Oxford
I. M. Anderson
Affiliation:
University of Manchester, Manchester
*
∗Correspondence
Get access Rights & Permissions [Opens in a new window]

Abstract

The hypothermic, growth hormone and corticotrophin (ACTH) responses to the 5-HT1A receptor agonist buspirone (30 mg orally) were measured in 20 unmedicated patients with major depression and 20 healthy controls. Compared with the controls, the hypothermic responses of the depressed patients to buspirone were significantly attenuated, particularly in patients with melancholic depression. In contrast, the responses of growth hormone and ACTH to buspirone were unchanged. The data suggest that major depression may be associated with impaired sensitivity of 5-HT1A autoreceptors but that the function of the post-synaptic 5-HT1A receptors that mediate growth hormone and ACTH release is unaltered. Within the limitations that attend the use of buspirone as a 5-HT1A probe, our data suggest that the decrement in serotonin neurotransmission at post-synaptic 5-HT1A receptors in depression is due to decreased serotonin release rather than impaired responsivity of post-synaptic 5-HT1A receptors.

Type
Peer Review
Information
The British Journal of Psychiatry , Volume 164 , Issue 3 , March 1994 , pp. 372 - 379
Copyright
Copyright © 1994 The Royal College of Psychiatrists 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Amsterdam, J. D., Maislin, G., Abelman, E., et al (1986) Adrenocortical responsiveness to the ACTH stimulation test in depressed patients and healthy volunteers. Journal of Affective Disorder, 11, 265–274.CrossRefGoogle Scholar
Amsterdam, J. D., Maislin, G., Winokur, A., et al (1987) Pituitary and adrenocortical responses to the ovine corticotropin releasing hormone in depressed patients and healthy volunteers. Archives of General Psychiatry, 44, 775–781.CrossRefGoogle Scholar
Anderson, I. M., Cowen, P. J. & Graham-Smith, D. G. (1990) The effects of gepirone on neuroendocrine function and temperature in humans. Psychopharmacology, 100, 498–503.Google Scholar
Anderson, I. M., Cowen, P. J. (1992) Effect of pindolol on endocrine and temperature responses to buspirone in healthy volunteers. Psychopharmacology, 106, 428–432.CrossRefGoogle ScholarPubMed
Andrade, R. & Nicoll, R. A. (1987) Pharmacologically distinct action of serotonin on single pyramidal neurons of the rat hippocampus recorded in vitro. Journal of Physiology, 394, 99–124.Google Scholar
Beck, A. T., Ward, C. H., Mendelson, M., et al (1961) An inventory for measuring depression. Archives of General Psychiatry, 4, 561–567.Google Scholar
Bianchi, G. & Garattini, S. (1988) Blockade of alpha2-adreno-ceptors by l-(2-pyrimidinyl)-piperazine (PmP) in vivo and its relation to the activity of buspirone. European Journal of Pharmacology, 147, 343–350.Google Scholar
Blier, P., De Montigny, C. & Chaput, Y. (1990) Modifications of the serotonergic system by antidepressant treatments: implications for the therapeutic response in major depression. Journal of Clinical Psychopharmacology, 7, 24S–35S.Google Scholar
Boyce, M. J., Hinze, C., Haegele, K. D., et al (1991) Initial studies in man to characterise MDL 73,005EF, a novel 5-HT1A receptor ligand and putative anxiolytic. In Serotonin: Molecular Biology, Receptors and Functional Effects (ed. Fozard, J. R.). Basel: Birkhäuser Verlag.Google Scholar
Carroll, B. J., Feinberg, M., Greden, J. F., et al (1981) A specific laboratory test for the diagnosis of melancholia. Archives of General Psychiatry, 38, 15–22.Google Scholar
Coccaro, E. F., Gabriel, S., Mahon, T., et al (1990) Preliminary evidence of a serotonin (5-HT-1-like) component of the prolactin response to buspirone challenge in humans. Archives of General Psychiatry, 47, 494–495.Google Scholar
Cowen, P. J. (1991) Serotonin receptor subtypes: implications for psychopharmacology. British Journal of Psychiatry, 159 (suppl. 12), 7–14.Google Scholar
Cowen, P. J. & Charig, E. M. (1987) Neuroendocrine responses to intravenous tryptophan in major depression. Archives of General Psychiatry, 44, 958–966.Google Scholar
Cowen, P. J., Anderson, I. M. & Grahame-Smith, D. G. (1990) Neuroendocrine effects of azapirones. Journal of Clinical Psychopharmacology, 10, 21S–25S.Google Scholar
Cryer, P. E. & Daughaday, W. H. (1977) Growth hormone. In Clinical Neuroendocrinology (eds L. Martini & G. M. Benner), pp. 243–277. New York: Academic Press.CrossRefGoogle Scholar
Deakin, J. F. W., Pennell, I., Upadhyaya, A. J., et al (1990) A neuroendocrine study of 5-HT function in depression: evidence for biological mechanisms of endogenous and psychosocial causation. Psychopharmacology, 101, 85–92.CrossRefGoogle ScholarPubMed
de Montigny, C., Blier, P. & Chaput, Y. (1984) Electrophysiologically identified serotonin receptors in the rat CNS: effect of antidepressant treatment. Neuropharmacology, 23, 1511–1520.Google Scholar
Eison, A. E. & Temple, D. L. (1986) Buspirone: review of its pharmacology and current perspectives on its mechanism of action. American Journal of Medicine, 80 (suppl. 3B), 1–9.Google Scholar
Gammans, R. E., Mayol, R. F. & Labudde, J. A. (1986) Metabolism and disposition of buspirone. American Journal of Medicine, 80 (suppl. 3B), 41–51.Google Scholar
Gilbert, F., Brazell, C., Tricklebank, M. D., et al (1988a) Relationship of increased food intake and plasma ACTH levels to 5-HT1A receptor activation in rats. Psychoneuroendocrinology, 13, 471–478.Google Scholar
Gilbert, F., Brazell, C., Tricklebank, M. D., et al (1988b) Activation of 5-HT1A receptor subtype increases rat plasma ACTH concentration. European Journal of Pharmacology, 147, 431–439.Google Scholar
Glue, P., Sellman, J. D., Joyce, P. R., et al (1988) The hypothermic response to clonidine is absent in alcohol withdrawal but returns in abstinence. Biological Psychiatry, 24, 102–104.Google Scholar
Gold, P. W., Chrousos, G., Kellner, C., et al (1984) Psychiatric implications of basic and clinical studies with corticotropin-releasing factor. American Journal of Psychiatry, 5, 619–627.Google Scholar
Goodwin, G. M., De Souza, R. J. & Green, A. R. (1987a) Attenuation by electroconvulsive shock and antidepressant drugs of the 5-HT1A receptor-mediated hypothermia and serotonin syndrome by 8-OH-DPAT in the rat. Psychopharmacology, 91, 500–505.Google Scholar
Goodwin, G. M., De Souza, R. J. & Green, A. R. et al (1987b) The pharmacology of the behavioural and hypothermic responses of rats to 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT). Psychopharmacology, 91, 506–511.CrossRefGoogle ScholarPubMed
Hamilton, M. (1967) Development of a rating scale for primary depressive illness. British Journal of Social and Clinical Psychology, 6, 278–296.CrossRefGoogle ScholarPubMed
Heninger, G. R., Charney, D. S. & Sternberg, D. (1984) Serotonergic function in depression: prolactin response to intravenous tryptophan in depressed patients and healthy controls. Archives of General Psychiatry, 41, 398–402.CrossRefGoogle Scholar
Hillegaart, V. (1991) Effects of local application of 5-HT and 8-OHDPAT into the dorsal and median raphe nuclei on core temperature in the rat. Psychopharmacology, 103, 291–296.CrossRefGoogle Scholar
Hjorth, S. (1985) Hypothermia in the rat induced by the potent serotoninergic agent 8-OH-DPAT. Journal of Neural Transmission, 61, 131–135.Google Scholar
Hutson, P., Donohoe, T. P. & Curzon, G. (1987) Hypothermia induced by the putative 5-HT1A agonists LY 165163 and 8-OHDPAT is not prevented by 5-HT depletion. European Journal of Pharmacology, 143, 221–228.Google Scholar
Koenig, J. I., Meltzer, H. Y. & Gudelsky, G. A. (1988) 5-Hydroxytryptamine1A receptor-mediated effects of buspirone, gepirone and ipsapirone. Pharmacological and Biochemical Behaviour, 29, 711–715.Google Scholar
Koyama, T. & Meltzer, H. Y. (1986) A biochemical and neuroendocrine study of the serotonergic system in depression. In New Results in Depression Research (eds H. Hippius, G. L. Klerman & N. Matussek), pp. 169–188. Berlin: Springer-Verlag.Google Scholar
Lesch, K. P. (1992) 5-HT1A receptor responsivity in anxiety disorders and depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 15, 723–733.Google Scholar
Lesch, K. P., Rupprecht, R., Poten, B., et al (1989) Endocrine responses to 5-hydroxytryptamine-1A receptor activation by ipsapirone in humans. Biological Psychiatry, 26, 203–205.Google Scholar
Lesch, K. P., Sohnle, K., Poten, B., et al (1990a) Corticotropin and cortisol secretion following central 5-hydroxytryptamine-1A (5-HT1A) receptor activation: effects of 5-HT receptor and beta-adrenoceptor antagonists. Journal of Clinical Endocrinology Metabolism, 70, 670–674.Google Scholar
Lesch, K. P., Poten, B., Sohnle, K., et al (1990b) Pharmacology of the hypothermic response to 5-HT1A receptor activation in humans. European Journal of Clinical Pharmacology, 39, 17–19.Google Scholar
Lesch, K. P., Mayer, S., Disselkamp-Tietze, J., et al (1990c) Subsensitivity of the 5-hydroxytryptamine (5-HT1A) receptor-mediated hypothermic response to ipsapirone in unipolar depression. Life Science, 46, 1271–1277.Google Scholar
Lesch, K. P., Mayer, S., Disselkamp-Tietze, J., et al (1990d) 5-HT1A receptor responsivity in unipolar depression: evaluation of ipsapirone-induced ACTH and cortisol secretion in depressed patients. Biological Psychiatry, 28, 620–628.Google Scholar
Lesch, K. P., Disselkamp-Tietze, J. & Schmidtke, A. (1990e) 5-HT1A receptor function in unipolar depression: effect of chronic amitriptyline treatment. Journal of Neural Transmission, 180, 157–161.Google Scholar
McMillen, B. A. (1985) Comparative chronic effects of buspirone or neuroleptics on rat brain dopaminergic neurotransmission. Journal of Neural Transmission, 64, 1–12.Google Scholar
McMillen, B. A. Matthews, R. T., Sanghera, M. K., et al (1983) Dopamine receptor antagonism by the novel anti-anxiety drug, buspirone. Journal of Neuroscience, 3, 733–738.Google Scholar
Meltzer, H. Y., Gudelsky, G. A., Lowy, M. T., et al (1991) Neuroendocrine effects of buspirone: mediation by dopaminergic and serotonergic mechanisms. In Buspirone: Mechanisms and Clinical Aspects (eds G. Tunnicliff, A. S. Eison, O. P. Taylor), pp. 177–192. San Diego, California: Academic Press.Google Scholar
Miller, H. L., Delgado, P. L., Fischette, C. T., et al (1990) Neuroendocrine effects of tandospirone (SM-3997) in healthy subjects. ACNP Annual Meeting, p. 191 (abstract).Google Scholar
Nichols, G. A. & Kucha, D. H. (1972) Oral measurements. American Journal of Nursing, 72, 1091–1093.Google Scholar
Peroutka, S. J. (1988) 5-Hydroxytryptamine receptor subtypes. Annual Review of Neuroscience, 11, 45–60.Google Scholar
Price, L. H., Charney, D. S., Delgado, P. L., et al (1991) Serotonin function and depression. Neuroendocrine and mood responses to intravenous tryptophan in depressed patients and healthy comparison subjects. Archives of General Psychiatry, 148, 1518–1525.Google Scholar
Smith, C. E., Ware, C. J. & Cowen, P. J. (1990) Pindolol decreases prolactin and growth hormone responses to intravenous l-tryptophan. Psychopharmacology, 103, 140–142.Google Scholar
Sprouse, J. S. & Aghajanian, G. K. (1987) Electrophysiological responses of serotonergic dorsal raphe neurones to 5-HT1A and 5-HT1B agonists. Synapse, 1, 3–9.CrossRefGoogle Scholar
Sprouse, J. S. & Aghajanian, G. K. (1988) Responses of hippocampal pyramidal cells to putative serotonin 5-HT1A and 5-HT1B receptor agonists: a comparative study with dorsal raphé neurones. Neuropharmacology, 27, 707–715.Google Scholar
Van de Kar, L. D. (1991) Neuroendocrine pharmacology of serotonergic neurones. Annual Review of Pharmacology and Toxicology, 31, 289–320.Google Scholar
Willoughby, J. O., Menadue, M. F. & Liebelt, H. (1987) Activation of serotonin receptors in the medial basal hypothalamus stimulates growth hormone secretion in the unanesthetised rat. Brain Research, 404, 319–322.Google Scholar
Yocca, F. D. (1990) Neurochemistry and neurophysiology of buspirone and gepirone: interactions at presynaptic and post-synaptic 5-HT1A receptors. Journal of Clinical Psychopharmacology, 10, 6S–12S.Google Scholar
Young, A., MacDonald, L., St John, H., et al (1992) The effects of corticosterone on 5-HT1A receptor function in rodents. Neuropharmacology, 31, 433–438.Google Scholar
Submit a response

eLetters

No eLetters have been published for this article.