Skip to main content
SpringerLink
Log in

Chronic imipramine treatment normalizes levels of tyrosine hydroxylase in the locus coeruleus of chronically stressed rats

  • Original Investigations
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Previous studies have demonstrated that chronic stress increases and antidepressant treatments decrease levels of tyrosine hydroxylase (TH) in locus coeruleus (LC). In the present study, the influence of chronic antidepressant treatment on the induction of TH immunoreactivity in response to cold stress is examined. It was found that chronic imipramine pretreatment (18 days) attenuated the induction of TH in response to cold stress, resulting in levels of TH immunoreactivity not different from control. In contrast, imipramine pretreatment for 1 or 7 days was not sufficient to normalize the stress-induced elevation of TH immunoreactivity. These findings raise the possibility that the therapeutic action of antidepressants may be derived, in part, from the ability of these treatments to normalize levels of TH and thereby the function of the NE neurotransmitter system under conditions of stress.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

LC:

locus coeruleus

NE:

norepinephrine

TH:

tyrosine hydroxylase

References

  • Adell A, Garcia-Marquez C, Armario A, Gelpi E (1988) Chronic stress increases serotonin and noradrenaline in rat brain and sensitizes their responses to a further acute stress. J Neurochem 50:1678–1681

    PubMed  Google Scholar 

  • Adell A, Garcia-Marquez C, Armario A, Gelpi E (1989) Chronic administration of chlomipramine prevents the increase in serotonin and noradrenaline induced by chronic stress. Psychopharmacology 99:22–26

    Article  PubMed  Google Scholar 

  • Blier P, De Montigny C (1985) Serotonergic but not noradrenergic neurons in rat central nervous system adapt to long-term treatment with monoamine oxidase inhibitors. Neuroscience 16:949–955

    Article  PubMed  Google Scholar 

  • Breslau N, Davis GC (1986) Chronic stress and major depression. Arch Gen Psychiatry 43:309–314

    PubMed  Google Scholar 

  • Dohrenwend BP, Dohrenwend BS (1980) Psychiatric disorders and susceptability to stress: reactions to stress of varying magnitudes and varying origins. In: Robbins LN, Wing JK (eds) The social consequences of psychiatric disorders. Brunzer/Mazel, New York

    Google Scholar 

  • Gold PW, Goodwin FK, Chrousos GP (1988) Clinical and biochemical manifestations of depression: relation to the neurobiology of stress. N Engl J Med 319:348–353

    PubMed  Google Scholar 

  • Guidotti A, Costa E (1977) Trans-synaptic regulation of tyrosine 3-mono-oxygenase biosynthesis in rat adrenal medulla. Biochem Pharmacol 26:815–823

    Article  Google Scholar 

  • Guitart X, Hayward M, Nisenbaum LK, Beitner-Johnson D, Haycock JW, Nestler EJ (1990) Identification of MARPP-58, a morphine and cyclic AMP-regulated phosphoprotein of 58 kDa, as tyrosine hydroxylase: evidence for regulation of its expression by chronic morphine in the rat locus coeruleus. J Neurosci 10:2649–2659

    PubMed  Google Scholar 

  • Huang J, Maas JW, Hu GH (1979) The time course of noradrenergic pre- and postsynaptic activity during chronic desipramine treatment. Eur J Pharmacol 68:41–47

    Article  Google Scholar 

  • Katz RJ (1981) Animal model of depression: effects of electroconvulsive shock therapy. Neurosci Biobehav Rev 5:273–277

    Article  PubMed  Google Scholar 

  • Katz RJ (1982) Animal model of depression: pharmacological sensitivity of a hedonic deficit. Pharmacol Biochem Behav 16:965–968

    Article  PubMed  Google Scholar 

  • Katz RJ, Baldrighi G (1982) A further parametric study of imipramine in an animal model of depression. Pharmacol Riochem Behav 16:969–972

    Article  Google Scholar 

  • Katz RJ, Hersh S (1981) Amitriptyline and scopolamine in an animal model of depression. Neurosci Biobehav Rev 5:265–271

    Article  PubMed  Google Scholar 

  • Katz RJ, Sibel M (1982a) Animal model of depression: tests of three structurally and pharmacologically novel antidepressant compounds. Pharmacol Biochem Behav 16:973–977

    Article  PubMed  Google Scholar 

  • Katz RJ, Sibel M (1982b) Further analysis of the specificity of a novel animal model of depression-effect of an antihistaminic, antipsychotic and anxiolytic compound. Pharmacol Biochem Behav 16:979–982

    Article  PubMed  Google Scholar 

  • Katz RJ, Roth KA, Schmaltz K (1981) Amphetamine and tranylcypromine in an animal model of depression: pharmacological specificity of the reversal effect. Neurosci Biobehav Rev 5:259–264

    Article  PubMed  Google Scholar 

  • Loughlin SE, Foote SE, Grzanna R (1986) Efferent projections of nucleus locus coeruleus: morphologic subpopulations have different efferent targets. Neuroscience 18:307–319

    Article  PubMed  Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randell RJ (1951) Protein reagent with the folin phenol reagent. J Biol Chem, 193:256–275

    Google Scholar 

  • Loyd C (1980) Life events and depressive disorders reviewed. Arch Gen Psychiatry 37:541–548

    PubMed  Google Scholar 

  • Melia KR, Duman RS (1991) Involvement of corticotropin-releasing factor in chronic stress regulation of the brain noradrenergic system. Proc Natl Acad Sci USA 88:8382–8386

    PubMed  Google Scholar 

  • Melia KR, Rasmussen K, Terwilliger RZ, Haycock JW, Nestler EJ, Duman RS (1992) Coordinate regulation of the cyclic AMP system with firing rate and expression of tyrosine hydroxylase in the rat locus coeruleus: effects of chronic stress and drug treatments. J Neurochem 58:494–502

    PubMed  Google Scholar 

  • Nestler EJ, McMahon A, Sabban EL, Tallman JF, Duman RS (1990) Chronic antidepressant administration decreases the expression of tyrosine hydroxylase in the rat locus coeruleus. Proc Natl Acad Sci USA 87:7522–7526

    PubMed  Google Scholar 

  • Rabkin JG (1982) Stress and psychiatric disorders. In: Goldberg L, Breznitz S (eds) Handbook of stress. Free Press, New York

    Google Scholar 

  • Richard F, Faucon-Biguet N, Labatut R, Rollet D, Mallet J, Buda M (1988) Modulation of tyrosine hydroxylase gene expression in rat brain and adrenals by exposure to cold. J Neurosci Res 20:32–37

    Article  PubMed  Google Scholar 

  • Roffler-Tarlov S, Schildkraut JJ, Draskoczy PR (1973) Effects of acute and chronic administration of desmethylimipramine on the content of norepinephrine and other monoamines in the rat brain. Biochem Pharmacol 22:2923–2926

    Article  PubMed  Google Scholar 

  • Segal DS, Kuczenski R, Mandell AJ (1974) Theoretical implications of drug-induced adaptive regulation for a biogenic amine hypothesis of affective disorders. Biol Psychiatry 9:147–159

    PubMed  Google Scholar 

  • Stone EA (1975) Stress and catecholamines. In: Freidhof AJ (ed) Catecholamines and behavior. Plenum Press, New York

    Google Scholar 

  • Stone EA, McCarty R (1983) Adaptation to stress: tyrosine hydroxylase activity and catecholamine release. Neurosci Biobehav Rev 7:29–34

    Article  PubMed  Google Scholar 

  • Thoenen H (1970) Induction of tyrosine hydroxylase in peripheral and central adrenergic neurons by cold exposure of rats. Nature 228:861–862

    Article  PubMed  Google Scholar 

  • Valentino RJ, Wehby RG (1988) Corticotropin-releasing factor: evidence for a neurotransmitter role in the locus coeruleus during hemodynamic stress. Neuroendocrinology 48:674–677

    PubMed  Google Scholar 

  • Valentino RJ, Curtis AL, Parris DG, Wehby RG (1990) Antidepressant actions on brain noradrenergic neurons. J Pharmacol Exp Ther 253:833–840

    PubMed  Google Scholar 

  • Vernikos J, Dallman MF, Bonner C, Katzen A, Shinsako J (1982) Pituitary adrenal function in rats chronically exposed to cold. Endocrinology 110:413–420

    PubMed  Google Scholar 

  • Willner P (1984) The validity of animal models of depression. Psychopharmacology 83:1–6

    Google Scholar 

  • Winokur G (1979) General discussion. In: Barret JE (ed) Stress and mental disorders. Raven Press, New York

    Google Scholar 

  • Zigmond RE (1980) The long term regulation of ganglionic tyrosine hydroxylase by preganglionic nerve activity. Fed Proc 39:3003–3008

    PubMed  Google Scholar 

  • Zigmond RE, Schon F, Iversen LL (1974) Increased tyrosine hydroxylase activity in the locus coeruleus of rat brain stem after reserpine treatment and cold stress. Brain Res 70:547–555

    Article  PubMed  Google Scholar 

  • Zigmond RE, Schwarzschild MA, Rittenhouse AR (1989) Acute regulation of tyrosine hydroxylase by nerve activity and by neurotransmitters via phosphorylation. Annu Rev Neurosci 12:415–461

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Molecular Psychiatry, Department of Psychiatry, Yale University School of Medicine and the Ribicoff Research Facilities of the Connecticut Mental Health Center, 34 Park Street, 06508, New Haven, CT, USA

    Kathleen R. Melia, Eric J. Nestler & Ronald S. Duman

Authors
  1. Kathleen R. Melia
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eric J. Nestler
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ronald S. Duman
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Melia, K.R., Nestler, E.J. & Duman, R.S. Chronic imipramine treatment normalizes levels of tyrosine hydroxylase in the locus coeruleus of chronically stressed rats. Psychopharmacology 108, 23–26 (1992). https://doi.org/10.1007/BF02245280

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02245280

Key words

Search

Navigation