Skip to main content Accessibility help
×
Home
Hostname: page-component-55b6f6c457-b6fb2 Total loading time: 0.218 Render date: 2021-09-25T13:26:07.548Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "metricsAbstractViews": false, "figures": true, "newCiteModal": false, "newCitedByModal": true, "newEcommerce": true, "newUsageEvents": true }

Stress, norepinephrine and depression

Published online by Cambridge University Press:  24 June 2014

Brian E. Leonard*
Affiliation:
Pharmacology Department, National University of Ireland, Galway, Department of Psychiatry, Academic Hospital, University of Maastricht, Postbus 5800, 6202 Maastricht, the Netherlands

Abstract

Experimental and clinical evidence implicates stress as a major predisposing factor in depression and other severe psychiatric disorders. In this review, evidence is presented to show how the impact of stress on the central sympathetic system leads to changes in the endocrine, immune and neurotransmitter axes which underlie the main clinical symptoms of depression. Thus it can be shown that the noradrenergic system is dysfunctional in depression, a situation which reflects the chronic hypersecretion of glucocorticoids and inflammatory mediators within the brain in addition to an enhanced activity of the locus ceruleus. With regard to the actions of antidepressants in modulating the stress response and alleviating depression it is now evident that, irrespective of the presumed specificity of the antidepressants for the noradrenergic or serotonergic systems, they all normalize noradrenergic function. This action is due partly to the regulation of tyrosine hydroxylase activity in the locus ceruleus but also enhances neuronal sprouting which counteracts the neurodegenerative effects of chronic stress.

Type
Original Article
Copyright
Copyright © Blackwell Munksgaard 2002

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

Irwin, M. Psychoneuroimmunology of depression. In: Bloom, KE, Kupfer, DJ, eds. Psychopharmacology: the fourth generation of progress. New York: Raven Press, 1995: 983998. Google Scholar
Melia, KR, Rasmussen, K, Terwilliger, RZ, Haycock, JW, Nestler, EJ, Duman, RS. Co-ordinate regulation of the cyclic AMP system with firing rate and expression of tyrosine hydroxlase in the rat locus cerulaeus: effect of chronic stress and drug treatment. J Neurochem 1992;58: 494502.CrossRefGoogle Scholar
Holets, VR. The anatomy and function of noradrenaline in the mammalian brain. In: Heal, DJ, Marsden, CA, eds. The pharmacology of noradrenaline in the CNS. Oxford: Oxford University Press, 1990: 140. Google Scholar
Nutt, DJ, Lalies, MD, Lione, LA, Hudson, AL. Noradrenergic mechanisms in the prefrontal cortex. J Psychopharmacol 1997;11: 163168.CrossRefGoogle ScholarPubMed
Nutt, DJ, Holman, RB, Thomas, DN. Noradrenergic mechanisms in anxiolytic and antidepressant drug action. In: Elliott, MJ, ed. Experimental approaches to anxiety and depression. Chichester: John Wiley and Sons, 1992: 101106. Google ScholarPubMed
Green, AR. The effects of antidepressant drugs on noradrenergic receptor mechanisms in the CNS. In: Heal, DJ, Marsden, CA, eds. The pharmacology of noradrenaline in the CNS. Oxford: Oxford University Press, 1990: 316348. Google Scholar
Stanford, C, Nutt, DJ, Cowen, PJ. Comparison of the effects of chronic desipramine administration on alpha 2 and beta-adrenoceptors in different regions of the brain. Neuroscience 1983;8: 161164.CrossRefGoogle Scholar
Ordway, GA, Smith, KS, Haycock, JW. Elevated tyrosine hydroxylase in the locus ceruleus of suicide victims. J Neurochem 1994;62: 680685.CrossRefGoogle Scholar
Nestler, EJ, McMahon, A, Subban, EL, Tallman, JF, Duman, RS. Chronic antidepressant administration decreases the expression of tyrosine hydroxylase in rat locus ceruleus. Proc Natl Acad Sci USA 1990;87: 75227526.CrossRefGoogle Scholar
Valentino, RJS, Curtis, AL, Parris, DG, Wehby, RG. Antidepressant actions on brain noradrenergic neurons. J Pharmacol Exp Ther 1990;253: 833840.Google Scholar
Brady, LS. Stress, antidepressant drugs and the locus ceruleus. Brain Res Bull 1994;35: 545556.CrossRefGoogle Scholar
Redmond, AM, Leonard, BE. An evaluation of the role of the noradrenergic system in the neurobiology of depression: a review. Hum Psychopharmacol 1997;12: 407430. 3.0.CO;2-1>CrossRefGoogle Scholar
Iversen, LL, Rossor, MN, Reynolds, GP. Loss of pigmented dopamine beta-hydroxylase positive cells from the locus ceruleus in senile dementia of the Alzheimer type. Neurosci Lett 1983;39: 95100.CrossRefGoogle Scholar
German, DC, Walker, BS, Manaye, K, Smith, WK, Woodward, DJ, North, AJ. The human locus ceruleus: computer reconstruction of cellular distribution. J Neurosci 1988;8: 17761789.Google ScholarPubMed
Gaspar, P, Duyckaerts, C, Alvarez, C, Javoy-Agid, F, Berger, B. Alterations of dopamine and noradrenaline innervations in their motor cortex in panic disorder. Ann Neurol 1991;30: 365374.CrossRefGoogle Scholar
Arnstein, AFT, Leslie, FM. Behavioural and receptor binding analysis of the alpha 2 adrenergic agonist UK-14304. Evidence for cognitive enhancement of an alpha 2 adrenoceptor subtype. Neuropharmacology 1991;30: 12791289.CrossRefGoogle Scholar
Aoki, C, Go, CG, Venkateson, C, Kurose, H. Perikaryal and synaptic localization of alpha 2A adrenergic receptor-like immunoreactivity. Brain Res 1994;650: 181204.CrossRefGoogle Scholar
Cai, JX, Ma, Y, Xu, L, Hu, X. Reserpine impairs spatial working memory performance in monkeys: reversal by the alpha 2 adrenergic agonist clonidine. Brain Res 1993;614: 191196.Google ScholarPubMed
Arnstein, AFT. Catechol regulation of the frontal cortex. J Psychopharmacology 1997;11: 151162. CrossRefGoogle Scholar
Arnstein, AFT, Cai, JX, Goldman-Rakic, PS. The alpha 2 agonist guanfacine improves memory in aged monkeys without sedative or hypotensive side effects: evidence for alpha 2 subtypes. J Neurosci 1988;8: 42874298.Google Scholar
Arnstein, AFT, Contant, TA. Alpha 2 adrenergic agonists decrease distractability in aged monkeys performing the delayed response task. Psychopharmacology 1992;108: 159169.CrossRefGoogle Scholar
Moffoot, A, O'Carroll, RE, Murray, C, Dougall, N, Bbmeier, K, Goodwin, GM. Clonidine infusion increases uptake of Tc-exametrazmine in the anterior cingulated cortex in Korsakoff's psychosis. Psychol Med 1994;24: 5361.CrossRefGoogle Scholar
Barkley, RA, Grodzinsky, G, Dupaul, GJ. Frontal lobe function in attention deficit disorder with, and without, hyperactivity: a review and research report. J Abnorm Child Psychol 1992;20: 163188.CrossRefGoogle ScholarPubMed
Buzsaki, G, Kennedy, B, Solt, VB, Ziegler, M. Noradrenergic control of thalamic oscillation: the role of alpha 2 receptors. Eur J Pharmacol 1991;203: 222229. Google Scholar
Davies, BJ, Wellman, PJ. Effects on ingestive behaviour in rats of the alpha 1 adrenoceptor agonist cirazoline. Eur J Pharmacol 1992;210: 1116.CrossRefGoogle ScholarPubMed
Ashton-Jones, G, Shipley, MT, Chouvet, G. Afferent regulation of locus ceruleus neurons: anatomy, physiology and pharmacology. Prog Brain Res 1991;88: 4775.CrossRefGoogle Scholar
Ennis, M, Shipley, MT, Aston-Jones, G, Williams, JT. Afferent control of locus ceruleus: differential regulation by shell and core outputs. Proceedings of the 8th Catecholamine Symposium. 1997: 67. Google Scholar
Rajkowski, J, Kubiale, P, Ivanova, S, Aston-Jones, G. State related activity and reactivity of locus ceruleus neurons in behaving monkeys. Proceedings of the 8th Catecholamine Symposium. 1997: 95. Google Scholar
Checkley, SA, Slade, AP, Shur, E. Growth hormone and other responses to clonidine in patients with endogenous depression. Br J Psychiatry 1981;138: 5155.CrossRefGoogle ScholarPubMed
Charney, DS, Heninger, GR, Sternberg, DE, Hafstad, KM, Giddings, S, Landis, DH. Adrenergic receptor sensitivity in depression: effects of clonidine in depressed patients and healthy subjects. Arch Gen Psychiatry 1982;39: 290294.CrossRefGoogle ScholarPubMed
Mitchell, PB, Bearn, JA, Corn, TH, Checkley, SA. Growth hormone response to clonidine after recovery in patients with endogenous depression. Br J Psychiatry 1988;152: 3438.CrossRefGoogle ScholarPubMed
Mann, JJ, Stanley, M, McBride, PA, McEwen, BS. Increased 5HT 2 and beta adrenergic receptor binding in the frontal cortex of suicide victims. Arch Gen Psychiatry 1986;43: 954969.CrossRefGoogle Scholar
Meana, JJ, Garcia-Sevilla, JA. Increased alpha adrenoceptor density in the frontal cortex of depressed suicide victims. J Neural Transm 1987;70: 377381.CrossRefGoogle ScholarPubMed
Karege, F, Bovier, P, Hilleret, H, Gaillard, JM. Platelet alpha 2 adrenoceptor mediated primary aggregation and adenylate cyclase inhibition in depressed patients. Lancet 1993;381: 1029. CrossRefGoogle Scholar
Healy, D, Carnet, PA, Leonard, BE. Monoamine related markers of depression: changes following treatment. J Psychiatr Res 1983;17: 251260. CrossRefGoogle Scholar
Garcia-Sevilla, JA, Guimont, J, Garcia-Vallejo, P, Fuster, MJ. Biochemical and functional evidence of the supersensitive platelet alpha 2 receptors in major depression. Arch Gen Psychiatry 1986;43: 5157.Google Scholar
Butler, J, Leonard, BE. Postpartum depression and the effect of nomifensine treatment. Int J Psychopharmacol 1986;1: 244252. CrossRefGoogle Scholar
Piletz, JE, Halaris, A, Saran, A, Marler, MR. Desipramine lowers tritiated p-aminoclonidine binding in platelets of depressed patients. Arch Gen Psychiatry 1991;48: 813820.CrossRefGoogle ScholarPubMed
Manji, HK, Drevets, WC, Charney, DS. The cellular neurobiology of depression. Nat Med 2001;7: 541547.CrossRefGoogle Scholar
Jacoby, RJ, Levy, R. Computed tomography in the elderly. 3. Affective disorders. Br J Psychiatry 1980;136: 270275.CrossRefGoogle Scholar
Jacoby, RJ, Dolan, RJ, Levy, R, Baldy, R. Quantitative computed tomography in elderly depressed patients. Br J Psychiatry 1986;136: 270275. CrossRefGoogle Scholar
Alexopoulos, GS, Young, RC, Shindledecker, RD. Brain computerised tomography findings in depression and primary degenerative dementia. Biol Psychiatry 1992;31: 591599.CrossRefGoogle ScholarPubMed
Blats, BC, Sahakian, BJ, Levy, R. Cognitive performance in tests sensitive to frontal lobe dysfunction in the elderly depressed. Psychol Med 1996;26: 591603.Google Scholar
Coffey, CE, Wilkinson, WE, Weiner, RD, Richie, JC, Aque, M. The dexamthasone suppression test and quantitative cerebral anatomy in depression. Biol Psychiatry 1993;33: 442449.CrossRefGoogle Scholar
Coffey, CE, Wilkinson, WE, Weiner, RD, Parashes, IA. Quantitative cerebral anatomy in depression. Arch Gen Psychiatry 1993;50: 716.CrossRefGoogle Scholar
Konsman, J, Kelley, K, Dantzer, R. Temporal and spatial relationship between LPS-induced expression of Fos, IL-1 beta and inducible NO synthase in rat brain. Neuroscience 1999;89: 535548.CrossRefGoogle Scholar
Rajkowska, G. Post mortem studies in mood disorders indicate altered number of neurons and glial cells. Biol Psychiatry 2000;48: 766777.CrossRefGoogle Scholar
Kitayama, I, Nakamina, S, Yaga, T, Murase, S, Nomura, J, Kayahara, T, Nakans, K. Brain Res Bull 1994;35: 573580.CrossRefGoogle Scholar
Sapolsky, RM, Uno, H, Rebert, CS, Finch, CE. Hippocampal damage associated with prolonged glucocorticoid exposure in primates. J Neurosci 1990;10: 28972902.Google ScholarPubMed
Drevets, WC. Neuroimaging studies of mood disorders: implications for a neural model of major depression. Biol Psychiatry 2000;48: 813829.CrossRefGoogle Scholar
Calabrese, J, Skwerer, RG, Barna, B. Depression, immunocompetence and prostaglandins of the E series. Psychiatr Res 1986;17: 4447. CrossRefGoogle ScholarPubMed
Maes, M, Smith, R, Scharpe, S. The monocyte T-lymphocyte hypothesis of major depression. Psychoneuroendocrinology 1995;20: 111116.CrossRefGoogle Scholar
Nakamura, S. Antidepressants induce regeneration of catecholamine axon terminals of brain catecholamine neurons. Neuroreport 1990;2: 525528. CrossRefGoogle Scholar
Duman, RS, Heninger, GR, Nestler, EJ. A molecular and cellular theory of depression. Arch Gen Psychiatry 1997;54: 597606.CrossRefGoogle Scholar
Kelly, JP, Wrynn, AS, Leonard, BR. The olfactory bulbectonised rat as a model of depression: an update. Pharmacol Ther 1997;74: 299316.CrossRefGoogle ScholarPubMed
Valentino, RJS, Li, DD, Godse, D, Cheung, S. Brain noradrenergic neural activity affects dihydroxyphenylethylene glycol levels. Life Sci 1981;29: 13031307.Google Scholar
Dunn, AJ, Berridge, CW. CRF administration elevates a stress-like activation of cerebral catecholamine systems. Pharmacol Biochem Behav 1987;27: 685691.CrossRefGoogle Scholar
Song, C, Earley, B, Leonard, BE. Behavioural, neurochemical and immunological responses to CRF administration. Ann NY Acad Sci 1995;771: 5572.CrossRefGoogle Scholar
Berridge, CW, Dunn, AJ. Restraint stress induced changes in exploratory behaviour appears to be mediated by noradrenaline stimulated release of CRF. J Neurosci 1989;9: 35133521.Google Scholar
Charney, DG, Heninger, GR, Breier, A. Noradrenergic function in panic anxiety: effects of yohimbine in healthy subjects and patients with agoraphobia and panic disorder. Arch Gen Psychiatry 1984;41: 751768.CrossRefGoogle ScholarPubMed
Leonard, BE. Brain cytokines and the psychopathology of depression. In: Leonard, BE, ed. Antidepressants. Basel: Birkhauser-Verlag, 2001: 109120. CrossRefGoogle Scholar
Song, C, Lin, A, Banaccorso, S, Heide, C, Verkerk, R, Maes, M. The inflammatory response system and the availability of plasma tryptophan in patients with primary sleep disorders and major depression. J Affect Disord 1998;49: 211219.CrossRefGoogle ScholarPubMed
Van Dam, AM, Brouns, M, Louisse, S, Berkenbosch, F. Appearance of IL-1 in macrophages and in microglia in the brain of endotoxin treated rats: a pathway for the induction of sickness? Brain Res 1992;588: 291296.CrossRefGoogle ScholarPubMed
Turnbull, AV, Rivier, CL. Regualtion of the HPA axis by cytokines: actions and mechanisms of action. Physiol Rev 1999;79: 171.Google Scholar
Smith, RS. The macrophage theory of depression. Med Hypoth 1991;35: 298306. CrossRefGoogle Scholar
Dinan, TG. Glucocorticoids and the genesis of depressive illness: a psychobiological model. Br J Psychiatry 1994;164: 365371.CrossRefGoogle Scholar
Niimi, M, Sato, M, Wada, Y, Takahara, J, Kawanski, K. Effect of central and continuous I.V. injections of IL-1 beta on brain c-Fos expression in rats: involvement of prostaglandins. Neuroimmunology 1996;3: 8792. Google Scholar
8
Cited by

Send article to Kindle

To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Stress, norepinephrine and depression
Available formats
×

Send article to Dropbox

To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

Stress, norepinephrine and depression
Available formats
×

Send article to Google Drive

To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

Stress, norepinephrine and depression
Available formats
×
×

Reply to: Submit a response

Please enter your response.

Your details

Please enter a valid email address.

Conflicting interests

Do you have any conflicting interests? *