Skip to main content
Log in

Chronic administration of clomipramine prevents the increase in serotonin and noradrenaline induced by chronic stress

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

Abstract

The effects of chronic clomipramine administration (15 mg/kg daily for 23 days) on changes in serotonin (5-hydroxytryptamine, 5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and noradrenaline (NA) induced by chronic stress have been studied in the rat brain. Chronic stress increased 5-HT in midbrain, pons and hippocampus, 5-HIAA in frontal cortex, midbrain, pons and hippocampus, and NA in midbrain and striatum. Chronic clomipramine significantly decreased the levels of 5-HT in most regions. In hypothalamus, hippocampus and perhaps in frontal cortex this effect possibly reflects decreased synthesis caused by an action on presynaptic 5-HT receptors. However, in midbrain, pons and striatum decreased 5-HT could not be attributed to a decrease in its synthesis since 5-HIAA also increased. This drug treatment also reduced NA in all regions except the striatum. Nevertheless, conclusions on NA synthesis or turnover cannot be drawn since only NA levels were measured. When administered concurrently, chronic clomipramine prevented the increases in 5-HT, 5-HIAA and NA produced by chronic stress. These results are in good accordance with previous findings showing that chronic antidepressant treatment also prevented behavioural disturbances induced by chronic stress.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

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

    Google Scholar 

  • Adell A, Trullas R, Gelpí E (1988b) Time course of changes in serotonin and noradrenaline in rat brain after predictable or unpredictable shock. Brain Res 459:54–59

    Google Scholar 

  • Anisman H, Pizzino A, Sklar LS (1980) Coping with stress, norepinephrine depletion and escape performance. Brain Res 191:583–588

    Google Scholar 

  • Armario A, García-Marquez C, Adell A, Gelpí E (1988) Chronic shock increases serotoninergic activity in male rats. No relationship to adaptation of the pituitary-adrenal axis. In: Van Loon G, Kvetnansky R, Axelrod J (eds) Stress: neurochemical and humoral mechanisms. Gordon and Breach, New York (in press)

    Google Scholar 

  • Bliss EL, Ailion J, Zwanziger J (1968) Metabolism of norepinephrine, serotonin and dopamine in rat brain with stress. J Pharmacol Exp Ther 164:122–134

    Google Scholar 

  • Carlsson A, Lindqvist M (1978) Effects of antidepressant agents on the synthesis of brain monoamines. J Neural Transm 43:73–91

    Google Scholar 

  • Carlsson A, Corrodi H, Fuxe K, Hökfelt T (1969a) Effect of antidepressant drugs on the depletion of intraneuronal brain 5-hydroxytryptamine stores caused by 4-methyl-α-ethyl-meta-tyramine. Eur J Pharmacol 5:357–366

    Google Scholar 

  • Carlsson A, Corrodi H, Fuxe K, Hökfelt T (1969b) Effects of some antidepressant drugs on the depletion of intraneuronal brain catecholamine stores caused by 4,α-dimethyl-meta-tyramine. Eur J Pharmacol 5:367–373

    Google Scholar 

  • Carruba MO, Picotti GB, Zambotti F, Mantegazza P (1977) Effects of mazindol, fenfluramine and chlorimipramine on the 5-hydroxytryptamine uptake and storage mechanisms in rat brain: similarities and differences. Naunyn-Schmiedeberg's Arch Pharmacol 300:227–232

    Google Scholar 

  • Charney DS, Menkes DB, Heninger GR (1981) Receptor sensitivity and the mechanism of action of antidepressant treatment. Arch Gen Psychiatry 38:1160–1180

    Google Scholar 

  • Charney DS, Woods SW, Goodman WK, Heninger GR (1987) Serotonin function in anxiety. II. Effects of the serotonin agonist MCPP in panic disorder patients and healthy subjects. Psychopharmacology 92:14–24

    Google Scholar 

  • Culman J, Kiss A, Kvetnansky R (1984) Serotonin and tryptophan hydroxylase in isolated hypothalamic and brain stem nuclei of rats exposed to acute and repeated immobilization stress. Exp Clin Endocrinol 83:28–36

    Google Scholar 

  • Curzon G, Joseph MH, Knott PJ (1972) Effects of immobilization and food deprivation on rat brain tryptophan metabolism. J Neurochem 19:1967–1974

    Google Scholar 

  • Eschalier A, Montastruc JL, Devoize JL, Rigal F, Gaillard-Plaza G, Pechadre JC (1981) Influence of naloxone and methysergide on the analgesic effect of clomipramine in rats. Eur J Pharmacol 74:1–7

    Google Scholar 

  • File SE, Tucker JC (1984) Prenatal treatment with clomipramine: effects on the behaviour of male and female adolescent rats. Psychopharmacology 82:221–224

    Google Scholar 

  • Friedman E, Cooper TB (1983) Pharmacokinetics of chlorimipramine and its demethylated metabolite in blood and brain regions of rats treated acutely and chronically with chlorimipramine. J Pharmacol Exp Ther 225:387–390

    Google Scholar 

  • García-Marquez C, Armario A (1987) Interaction between chronic stress and clomipramine treatment in rats. Effects on exploratory activity, behavioral despair, and pituitary-adrenal function. Psychopharmacology 93:77–81

    Google Scholar 

  • Glavin GB (1985) Stress and brain noradrenaline: a review. Neurosci Biobehav Rev 9:233–243

    Google Scholar 

  • Glowinski J, Iversen LL (1966) Regional studies of catecholamines in the rat brain-I. The disposition of [3H]norepinephrine, [3H]dopamine and [3H]DOPA in various regions of the brain. J Neurochem 13:655–669

    Google Scholar 

  • Green AR (1987) Evolving concepts on the interaction between antidepressant treatments and monoamine neurotransmitters. Neuropharmacology 26:815–822

    Google Scholar 

  • Jesberger JA, Richardson JS (1985) Animal models of depression: parallels and correlates to severe depression in humans. Biol Psychiatry 20:764–784

    Google Scholar 

  • Kametani H, Nomura S, Shimizu J (1983) The reversal effect of antidepressants on the escape deficit induced by inescapable shock in rats. Psychopharmacology 80:206–208

    Google Scholar 

  • Katz RJ, Roth KA, Carroll BJ (1981) Acute and chronic stress effects on open field activity in the rat: implications for a model of depression. Neurosci Biobehav Rev 5:247–251

    Google Scholar 

  • Kennett GA, Dickinson SL, Curzon G (1985) Enhancement of some 5-HT-dependent behavioural responses following repeated immobilization in rats. Brain Res 330:253–263

    Google Scholar 

  • Kobayashi RM, Palkovits M, Kizer JS, Jacobowitz DM, Kopin IJ (1976) Selective alterations of catecholamines and tyrosine hydroxylase activity in the hypothalamus following acute and chronic stress. In: Usdin E, Kvetnansky R, Kopin IJ (eds) Catecholamines and stress. Pergamon Press, Oxford, pp 29–38

    Google Scholar 

  • Kramrcy NR, Delanoy RL, Dunn AJ (1984) Footshock treatment activates catecholamine synthesis in slices of mouse brain regions. Brain Res 290:311–319

    Google Scholar 

  • Lapierre YD, Rastogi RB, Singhal RL (1983) Fluvoxamine influences serotonergic system in the brain: neurochemical evidence. Neuropsychobiology 10:213–216

    Google Scholar 

  • Lehnert H, Reinstein DK, Strowbridge BW, Wurtman RJ (1984) Neurochemical and behavioral consequences of acute, uncontrollable stress: effects of dietary tyrosine. Brain Res 303:215–223

    Google Scholar 

  • Levine S, Madden IV J, Conner RL, Moskal JR, Anderson C (1973) Physiological and behavioral effects of prior aversive stimulation (preshock) in the rat. Physiol Behav 10:467–471

    Google Scholar 

  • Marco EJ, Meek JL (1979) The effects of antidepressants on serotonin turnover in discrete regions of rat brain. Naunyn-Schmiedeberg's Arch Pharmacol 306:75–79

    Google Scholar 

  • Platt JE, Stone EA (1982) Chronic restraint elicits a positive antidepressant response on the forced swim test. Eur J Pharmacol 82:179–181

    Google Scholar 

  • Porsolt RD, Le Pichon M, Jalfre M (1977) Depression: a new animal model sensitive to antidepressant treatments. Nature 266:730–732

    Google Scholar 

  • Prince CR, Anisman H (1984) Acute and chronic stress effects on performance in a forced-swim task. Behav Neural Biol 42:99–119

    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

    Google Scholar 

  • Roth KA, Mefford IM, Barchas JD (1982) Epinephrine, norepinephrine, dopamine and serotonin: differential effects of acute and chronic stress on regional brain amines. Brain Res 239:417–424

    Google Scholar 

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

    Google Scholar 

  • Sherman AD, Petty F (1982) Specificity of the learned helplessness animal model of depression. Pharmacol Biochem Behav 16:449–454

    Google Scholar 

  • Soblosky JS, Thurmond JB (1986) Biochemical and behavioral correlates of chronic stress: effects of tricyclic antidepressants. Pharmacol Biochem Behav 24:1361–1368

    Google Scholar 

  • Stone EA (1975) Stress and catecholamines. In: Friedhoff AJ (ed) Catecholamines and behavior. Plenum Press, New York, pp 31–66

    Google Scholar 

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

    Google Scholar 

  • Sugrue MF (1980) Changes in rat brain monoamine turnover following antidepressant administration. Life Sci 26:423–429

    Google Scholar 

  • Testa R, Angelico P, Abbiati GA (1987) Effect of citalopram, amineptine, imipramine and nortriptyline on stress-induced (footshock) analgesia in rats. Pain 29:247–255

    Google Scholar 

  • Thomas PC, Jones RB (1977) The effects of clomipramine and desmethylclomipramine on the in vitro uptake of radio-labelled 5-HT and noradrenaline into rat brain cortex slices. J Pharm Pharmacol 29:562–563

    Google Scholar 

  • Van Wijk M, Meisch JJ, Korf J (1977) Metabolism of 5-hydroxytryptamine and levels of tricyclic antidepressant drugs in rat brain after acute and chronic treatment. Psychopharmacology 55:217–223

    Google Scholar 

  • Weiss JM, Glazer HI, Pohorecky LA, Bailey WH, Schneider LH (1979) Coping behavior and stress-induced behavioral depression: studies of the role of brain catecholamines. In: Depue E (ed) The psychobiology of the depressive disorders: implications for the effects of stress. Academic Press, New York, pp 125–160

    Google Scholar 

  • Weiss JM, Goodman PA, Losito BG, Corrigan S, Charry JM, Bailey WH (1981) Behavioral depression produced by an uncontrollable stressor: relationship to norepinephrine, dopamine and serotonin levels in various regions of rat brain. Brain Res Rev 3:167–205

    Google Scholar 

  • Willner P (1984) The validity of animal models of depression. Psychopharmacology 83:1–16

    Google Scholar 

  • Wise CD, Berger BD, Stein L (1972) Benzodiazepines: anxiety-reducing activity by reduction of serotonin turnover in the brain. Science 177:180–183

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Adell, A., García-Marquez, C., Armario, A. et al. Chronic administration of clomipramine prevents the increase in serotonin and noradrenaline induced by chronic stress. Psychopharmacology 99, 22–26 (1989). https://doi.org/10.1007/BF00634447

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00634447

Key words

Navigation