Neuroendocrine Studies of α2-Adrenoceptor Function and the Mechanism of Action of Antidepressant Drugs

  • S. Checkley
Conference paper


This review examines clinical studies addressing three questions that are central to an understanding of α2-adrenoceptor function in depression: (a) Are the α2-adrenoceptors that mediate the growth hormone (GH) response to clonidine abnormal in depression? (b) Is the functional status of these receptors modified by chronic antidepressant treatment in man? And (c) what is the net effect on noradrenergic neurotransmission in man of chronic treatment with antidepressant drugs?


Growth Hormone Depressed Patient Antidepressant Drug Growth Hormone Response Melatonin Secretion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Ansseau M, von Frenckell R, Certontaine JL, Pappart P, Franck G, Timsit-Berthier M, Green V, Legros J J (1988) Blunted response of growth hormone to clonidine and apomorphine in endogenous depression. Br J Psychiatry 153: 65–71PubMedCrossRefGoogle Scholar
  2. Bearn JA, Franey C, Arendt J, Checkley SA (1989) A study of the effects of desipramine alone and in combination with L-triiodotryronine on 6-sulphatoxymelatonin excretion in depressed patients. Br J Psychiatry 152: 372–376CrossRefGoogle Scholar
  3. Boyer P, Davila M, Schaub C, Nassiet J (1986) Growth hormone response to clonidine stimulation in depressive states. Part I. Psychiatr Psychobiol 1: 189–195Google Scholar
  4. Casper R, Davis J (1977) Neuroendocrine and amine studies in affective illness. Psychoneuro-endocrinology 2: 105–113CrossRefGoogle Scholar
  5. Charney DS, Heninger GR, Sternberg DE (1982 a) Adrenergic receptor sensitivity and the mechanism of actions of antidepressant drugs. Arch Gen Psychiatry 39: 290–294Google Scholar
  6. Charney DS, Heninger GR, Sternberg DE (1982 b) Failure of chronic antidepressant treatment to alter growth hormone response to clonidine. Psychiatry Res 7: 135–138Google Scholar
  7. Checkley SA (1980) Neuroendocrine studies of nomoamine function in man: a review of basic theory and its application to the study of depressive illness. Psychol Med 10: 35–53PubMedCrossRefGoogle Scholar
  8. Checkley SA, Slade AP, Shur E (1981) Growth hormone and other responses to clonidine in patients with endogenous depression. Br J Psychiatry 138: 51–55PubMedCrossRefGoogle Scholar
  9. Checkley SA, Glass IB, Thompson C, Corn T, Robinson P (1984) The growth hormone response to clonidine in endogenous as compared to reactive depression. Psychol Med 14: 773–777PubMedCrossRefGoogle Scholar
  10. Checkley SA, Corn TH, Glass IB, Burton SW, Burke CA ( 1985 a) The responsiveness of central alpha adrenoceptors in depression. In: Deakin JFW (ed) The biology of depression. Gaskell, London, pp 110–119Google Scholar
  11. Checkley SA, Thompson C, Burton S, Franey C, Arendt J (1985 b) Clinical studies of the effect of (+) and (—) oxaprotiline upon noradrenaline uptake. Psychopharmacology 87: 116 - 118Google Scholar
  12. Corn TH, Hale AS, Thompson C, Bridges PJ, Checkley SA (1984a) A comparison of the growth hormone responses to Clonidine and apomorphine in the same patients with endogenous depression. Br J Psychiatry 144: 636–639PubMedCrossRefGoogle Scholar
  13. Corn TH, Thompson C, Checkley SA (1984 b) Effects of desipramine treatment upon central adrenoceptor function in normal subjects. Br J Psychiatry 145: 139–145Google Scholar
  14. Cowen PJ, Fräser S, Sammons R, Green AR (1983) Atenolol reduces plasma melatonin concentrations in man. Br J Clin Pharmacol 15: 579–581PubMedGoogle Scholar
  15. Cowen PJ, Green AR, Grahame-Smith DG, Braddock LE (1985) Plasma melatonin during desipramine treatment: evidence for changes in noradrenergic neurotransmission. Br J Clin Pharmacol 19: 799–805PubMedGoogle Scholar
  16. Dieguez C, Page MD, Scanion MF (1988) Growth hormone regulations and its alterations in disease states. Clin Endocrinol (Oxf) 28: 109–144Google Scholar
  17. Dolan RJ, Calloway SP (1986) The human growth hormone response to Clonidine: relationship to clinical and neuroendocrine profile in depression. Am J Psychiatry 143: 772–774PubMedGoogle Scholar
  18. Eden S, Eriksson E, Martin JB, Modign K (1981) Evidence for growth hormone releasing factor mediating alpha-adrenergic influence on growth hormone secretion in the rat. Neuroendocrinology 33: 24–27PubMedCrossRefGoogle Scholar
  19. Eriksson E, Eden S, Modign K (1981) Up and down regulation of central post-synaptic alpha2 adrenoreceptors reflected in the GH response to Clonidine in reserpine pretreated rats. Psychopharmacology 77: 327–331CrossRefGoogle Scholar
  20. Fraser A, Brown R, Kocsis J, Caroff S, Amsterdam J, Winokur A, Stokes P (1986) Patterns of melatonin rhythms in depression. Neural Trans (Suppl 21 ): 269–290Google Scholar
  21. Friedman E, Yocca FD, Cooper TB (1984) Antidepressant drugs with varying pharmacological profiles alter pineal beta adrenergic mediated function. J Pharmacol Exp Ther 228: 545–549PubMedGoogle Scholar
  22. Glass I, Checkley SA, Shur E, Dawling S (1982) The effect of desipramine upon central adrenergic function in depressed patients. Br J Psychiatry 141: 372–376PubMedCrossRefGoogle Scholar
  23. Golden RN, Markey SP, Risby ED, Rudorfer MV, Cowdry RW, Potter WZ (1988) Antidepressants reduce whole body norepinephrine while enhancing 6-hydroxymelatonin output. Arch Gen Psychiatry 45: 150–154PubMedCrossRefGoogle Scholar
  24. Goodwin GM, Fairburn CG, Cowen PJ (1987) The effects of dieting and weight loss on neuroendocrine responses to tryptophan, Clonidine and apomorphine in volunteers. Arch Gen Psychiatry 44: 952–957Google Scholar
  25. Hoehe M, Valido G, Matussek N (1986) Growth hormone response to Clonidine in endogenous depressive patients; evidence for a trait marker in depression. In: Shagass C, Josiassen EC, Bridger WH, Weiss KJ, Stoff D, Simpson GH (eds) Biological psychiatry developments in psychiatry. Elsevier, Amsterdam pp 862–864Google Scholar
  26. Horton RW, Katona CLE, Theodorou AE, Hale AS, Davies SL, Tunnicliffe C, Yamaguchi Y, Payket ES, Kelly JS (1986) Platelet radioligand binding and neuroendocrine challenge tests in depression. In: Murphy D (ed) Antidepressants and receptor function. CIBA Found Symp 123: 84–105Google Scholar
  27. Jimerson DC, Cutler NR, Post RM, Rey A, Gold A, Gold PW, Brown GM, Bunney WE (1984) Neuroendocrine responses to apomorphine in depressed patients and healthy control subjects. Psychiatry Res 13: –12PubMedCrossRefGoogle Scholar
  28. Klein DC (1978) The pineal gland: a model of neuroendocrine regulation. In: Reichlin S, Baldessarini RJ, Martin JB (eds) The hypothalamus. Raven, New York, pp 303–327Google Scholar
  29. Klein DC (1985) Photoneural regulation of the mammalian pineal gland. In: Short RV (ed) Photoperiodism melatonin and the pineal. CIBA Found Symp 117: 38–51Google Scholar
  30. Lechin F, van der Dijs B, Jakubowicz D, Camero RE, Villa S, Arocha L, Lechin AE (1985) Effects of Clonidine on blood pressure, noradrenaline, Cortisol, growth hormone and prolactin plasma levels in high and low intestinal tone depressed patients. Neuroendocrinology 41: 156–162Google Scholar
  31. Lesch KP, Laux G, Erb A, Pfüller H, Beckmann H (1987) Attenuated growth hormone response to growth hormone-releasing hormone in major depressive disorder. Biol Psychiatry 22: 1495–1499PubMedCrossRefGoogle Scholar
  32. Lewy AJ, Siever LJ, Uhde TW, Markey SP (1986) Clonidine reduces plasma melatonin levels. J Pharm Pharmacol 38: 555–556PubMedCrossRefGoogle Scholar
  33. Maany I, Mendels J, Frazer A, Brunswick D (1979) A study of growth hormone release in depression. Neuropsychobiology 5: 282–289PubMedCrossRefGoogle Scholar
  34. Matussek N, Ackenheil M, Hippius H, Muller F, Schroder H-T, Schultes H, Wasilewski B (1980) Effect of Clonidine on growth hormone release in psychiatric patients and controls. Psychiatry Res 2: 25–36PubMedCrossRefGoogle Scholar
  35. Meltzer HY, Kolakowska T, Fang VS, Fogg L, Robertson A, Lewine R, Strahlevitz M, Busch D (1984) Growth hormone and prolactin response to apomorphine in schizophrenia and the major affective disorders. Arch Gen Psychiatry 41: 512–519PubMedCrossRefGoogle Scholar
  36. Mitchell PB, Beam JA, Corn TH, Checkley SA (1988) Growth hormone response to Clonidine after recovery in patients from endogenous depression. Br J Psychiatry 152: 34–38PubMedCrossRefGoogle Scholar
  37. Murphy DL, Tamarkin L, Sunderland T, Garrick NA, Cohen R (1986) Human plasma melatonin is elevated during treatment with the monoamine oxidase inhibitors clorgyline and tranyleypramine but not pargyline. Psychiatry Res 17: 119–127PubMedCrossRefGoogle Scholar
  38. Palazidou E, Stahl SM, Franey C, Arendt J, Checkley SA (1989 a) Effects of the alpha adrenoceptor antagonist on melatonin in man. Psychoneuroendocrinology 14: 131–135Google Scholar
  39. Palazidou E, Sitzen A, Papadopoulous A, Checkley SA (1989 b) Effects of the alpha adrenoceptor antagonist Org 3770 on melatonin in man. Psychoneuroendocrinology 14: 131–135PubMedCrossRefGoogle Scholar
  40. Pelayo F, Dubocovitch ML, Langer SZ (1977) Regulation of noradrenaline release in the rat pineal gland through a negative feedback mechanism mediated by presynaptic alpha adrenoceptors. Eur J Pharmacol 45: 317–318PubMedCrossRefGoogle Scholar
  41. Racagnini G (1989) Receptor interactions and intracellular mechanisms in the actions of antidepressants. In: Leonard B (ed) Antidepressants thirty years on. Oxford University Press, Oxford (in press)Google Scholar
  42. Sack RL, Lewy AJ (1986) Desmethylimipramine treatment increases melatonin production in humans. Biol Psychiatry 21: 406–409PubMedCrossRefGoogle Scholar
  43. Siever LJ, Uhde TW, Silberman EK, Jimerson DC, Aloi JA, Post RM, Murphy DL (1982 a) Growth hormone response to Clonidine as a probe of noradrenergic receptor responsiveness in affective disorder patients and controls. Psychiatry Res 6: 171–183Google Scholar
  44. Siever LJ, Uhde TW, Insel TR, Roy BF, Murphy DL (1982 b) Growth hormone response to Clonidine unchanges by chronic chlorgyline treatment. Psychiatry Res 7: 139–144CrossRefGoogle Scholar
  45. Sulser F (1989) Molecular biological approaches to the mode of action of antidepressant drugs. In: Leonard B (ed) Antidepressants thirty years on. Oxford University Press, Oxford (in press)Google Scholar
  46. Sulser F, Vetulani J, Mobley PL (1978) Mode of action of antidepressant drugs. Biochem Pharmacol-27: 257–261Google Scholar
  47. Thompson C, Mezey G, Corn T, Franey C, English J, Arendt J, Checkley SA (1985) The effect of desipramine upon melatonin and Cortisol secretion in depressed and normal subjects. Br J Psychiatry 147: 714–722Google Scholar
  48. Uhde TW, Vittone BJ, Siever LJ, Kaye WH, Post RM (1986) Blunted growth hormone response to Clonidine in panic disorder patients. Biol Psychiatry 21: 1077–1081CrossRefGoogle Scholar
  49. Vanecek J, Sugden D, Weller J, Klein DC (1985) Atypical synergistic alpha- and beta- adrenergic regulation of adenosine 3’, 5’-monophosphate in cultured rat pinealocytes. Endocrinology 116: 2167–2173PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1990

Authors and Affiliations

  • S. Checkley
    • 1
  1. 1.Maudsley HospitalLondonUK

Personalised recommendations