Skip to main content
Log in

Nonlinear changes in activity and emotional reactivity scores following central noradrenergic lesions in rats

  • Published:
Psychopharmacologia Aims and scope Submit manuscript

Abstract

Two levels of permanent central norepinephrine depletion were obtained in rats by lesioning these neurons with small quantities of intraventricularly-applied 6-hydroxydopamine, and the effects of these lesions on a variety of standard tests of activity and emotional reactivity were studied. Both lesioned groups showed altered emotional reactivity; however, only the animals with less extensive lesions were hyperactive in running wheels, showed heightened shock-elicited aggression, were hyper-responsive to handling, and had a potentiated amphetamine-activation effect. It is suggested that these exaggerated behaviors reflected the sensitization and regeneration of partially lesioned noradrenergic circuits. These data are discussed in terms of the catecholamine hypothesis of depression.

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

  • Bhagat, B.: Effect of chronic cold stress on catecholamine levels in rat brain. Psychopharmacologia (Berl.) 16, 1–4 (1969)

    Google Scholar 

  • Blanchard, R. J., Blanchard, D. C.: Limbic lesions and reflexive fighting. J. comp. physiol. Psychol. 66, 603–605 (1968)

    Google Scholar 

  • Bliss, E. L., Ailiou, J., Zwanziger, J.: Metabolism of norepinephrine, serotonin, and dopamine in rat brain with stress. J. pharmacol. exp. Ther. 164, 122–134 (1968)

    Google Scholar 

  • Bloom, F. S., Algeri, S., Groppetti, A., Revuelta, A., Costa, E.: Lesions of central norepinephrine terminals with 6-OH-dopamine: biochemistry and fine structure. Science 166, 1284–1286 (1969)

    Google Scholar 

  • Breese, G. R., Traylor, T. D.: Effect of 6-hydroxydopamine on brain norepinephrine and dopamine: evidence for selective degeneration of catecholamine neurons. J. Pharmacol. exp. Ther. 174, 413–420 (1970)

    Google Scholar 

  • Brodie, H., Murphy, D., Goodwin, F., Bunney, W., Jr.: Catecholamines and mania: the effect of alpha-methyl-para-tyrosine on manic behavior and catecholamine metabolism. Clin. Pharmacol. Ther. 12, 218–224 (1971)

    Google Scholar 

  • Bunney, W. E., Jr., Davis, J. M.: Norepinephrine in depressive reactions. Arch. gen. Psychiat. 13, 483–494 (1965)

    Google Scholar 

  • Burkard, W. P., Jalfre, M., Blum, J.: Effect of 6-hydroxy-dopamine on behaviour and cerebral amine content in rats. Experientia (Basel) 25, 1295–1296 (1969)

    Google Scholar 

  • Carlsson, A., Fuxe, K., Hokfelt, T.: Failure of dopamine to accumulate in central noradrenaline neurons after depletion with diethyldithiocarbamate. J. Pharm. Pharmacol. 19, 481–483 (1967)

    Google Scholar 

  • Carlsson, A., Fuxe, K., Hokfelt, T., Lindqvist, M.: Histochemical and biochemical effects of diethyldithiocarbamate on tissue catecholamine. J. Pharm. Pharmacol. 18, 60–62 (1966)

    Google Scholar 

  • Corrodi, H., Fuxe, K., Ljungdahl, A., Ogren, S. D.: The effect of immobilization stress on the activity of central monoamine neurons. Life Sci. 7, 107–112 (1968)

    Google Scholar 

  • Corrodi, H., Fuxe, K., Ljungdahl, A., Ogren, S. D.: Studies on the action of some psychoactive drugs on central noradrenaline neurons after inhibition of dopamine-Β-hydroxylase. Brain Res. 24, 443–450 (1970)

    Google Scholar 

  • Dominic, J. A., Moore, K. E.: Supersensitivity to the central stimulant actions of adrenergic drugs following discontinuation of a chronic diet of alphamethyltyrosine. Psychopharmacologia (Berl.) 15, 96–101 (1969)

    Google Scholar 

  • Dominic, J. A., Moore, K. E.: Behavior and brain contents of catecholamines in mice during chronic administration of methyldopa. Neuropharmacology 10 565–570 (1971)

    Google Scholar 

  • Engelman, K., Horowitz, D., Jequier, E., Sjoerdsma, A.: Biochemical and pharmacologic effects of α-methyl-tyrosine in man. J. clin. Invest. 47, 577–594 (1968)

    Google Scholar 

  • Evetts, K. D., Uretsky, N. J., Iversen, L. L., Iversen, S. D.: Effects of 6-hydroxydopamine on CNS catecholamines, spontaneous motor activity, and amphetamine induced hyperactivity in rats. Nature (Lond.) 225, 961–962 (1970)

    Google Scholar 

  • Fleming, R. M., Clark, W. G., Fenster, E. D., Towne, J. C.: Single extraction method for the simultaneous fluorometric determination of serotonin, dopamine, and norepinephrine in brain. Analyl. Chem. 37, 692–696 (1965)

    Google Scholar 

  • Glick, S. D., Greenstein, S., Zimmerberg, B.: Facilitation of recovery by α-methyl-tyrosine after lateral hypothalamic damage. Science 178, 640–643 (1972)

    Google Scholar 

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

    Google Scholar 

  • Goldstein, M., Nakajima, K.: The effects of disulfiram on cateoholamine levels in the brain. J. pharm. Pharmacol. 157, 96–102 (1967)

    Google Scholar 

  • Hanson, C.: Evidence that the central action of (+)-amphetamine is mediated via catecholamines. Psychopharmacologia (Berl.) 10, 289–297 (1967)

    Google Scholar 

  • Hedreen, J., Chalmers, J.: Neuronal degeneration in rat brain induced by 6-hydroxydopamine: a histological and biochemical study. Brain Res. 47, 1–11 (1972)

    Google Scholar 

  • Jackson, H.: The Croonian Lectures on evolution and dissolution of the nervous system. Brit. med. J. 1884 I 591–593, 660–663, 703–707

    Google Scholar 

  • Katzman, R., Bjorklund, A., Owman, C., Stenevi, U., West, K.: Evidence for regenerative axon sprouting of central catecholamine neurons in the rat mesencephalon following electrolytic lesions. Brain Res. 25, 579–596 (1971)

    Google Scholar 

  • Kendell, E. R.: The classification of depressive illness. (Maudsely Monographs Nr 18) London: Oxford University Press 1968

    Google Scholar 

  • Klerman, G. L.: Clinical research in depression. Arch. gen. Psychiat. 24, 305–319 (1971)

    Google Scholar 

  • Lader, M. H.: Physical and physiological aspects of anxiety and depression. Brit. J. clin. Pract. 24, 55–59 (1970)

    Google Scholar 

  • Maickel, R. P., Cox, R. H., Saillant, J., Miller, F. P. A.: A method for the determination of serotonin and norepinephrine in discrete areas of rat brain. Int. J. Pharmacol. 7, 275–281 (1968)

    Google Scholar 

  • Merlis, J. K.: The effect of changes in the calcium content of the cerebrospinal fluid on spinal reflex activity in the dog. Amer. J. Physiol. 131, 67–72 (1940)

    Google Scholar 

  • Nakamura, K., Thoenen, H.: Increased irritability: a permanent behavior change induced in the rat by intraventricular administration of 6-hydroxydopamine. Psychopharmacologia (Berl.) 24, 359–372 (1972)

    Google Scholar 

  • Pellegrino, L. J., Cushman, A. J.: A sterotaxic atlas of the rat brain. New York: Appleton-Century-Crofts 1967

    Google Scholar 

  • Randrup, A., Munkvad, I.: Role of catecholamines in the amphetamine excitatory response. Nature (Lond.) 211, 540 (1966)

    Google Scholar 

  • Reid, W. D., Volicer, L., Smookler, H., Veaven, M. A., Brodie, B. B.: Brain amines and temperature regulation. Pharmacology 1, 329–344 (1968)

    Google Scholar 

  • Reis, D., Fuxe, K.: Brain norepinephrine: evidence that neuronal release is essential for sham rage behavior following brainstem transection in cat. Proc. nat. Acad. Sci. (Wash.) 64, 108–112 (1969)

    Google Scholar 

  • Richter, C. P.: Biological clocks in medicine and psychiatry. Springfield, Ill.: Ch. C. Thomas 1965

    Google Scholar 

  • Schildkraut, J. J.: The catecholamine hypothesis of affective disorders: a review of supporting evidence. Amer. J. Psychiat. 122, 509–522 (1965)

    Google Scholar 

  • Schildkraut, J. J., Kety, S. S.: Biogenic amines and emotion. Science 156, 21–30 (1967)

    Google Scholar 

  • Segal, D., Sullivan, J., Kuczenski, R., Mandell, A.: Effects of long-term reserpine treatment on brain tyrosine hydroxylase and behavioral activity. Science 173, 847–849 (1971)

    Google Scholar 

  • Simmonds, M. A., Uretsky, N. J.: Central effects of 6-hydroxy-dopamine on the body temperature of the rat. Brit. J. Pharmacol. 40, 630–638 (1970)

    Google Scholar 

  • Smith, C. B.: Effects of d-amphetamine upon brain amine content and locomotor activity of mice. J. Pharmacol. exp. Ther. 147, 96–102 (1965)

    Google Scholar 

  • Stein, L.: Psychopharmacological substrates of mental depression. In: S. Garattini and M. Dukes (Eds.): Proc. 1st. Int. Symp.: Antidepressant Drugs. Exerpta Medica 1967

  • Stolk, J. M., Rech, R. H.: Antagonism of d-amphetamine by alpha-methyl-l-tyrosine: behavioral evidence for the participation of catecholamine stores and synthesis in the amphetamine stimulant response. Neuropharmacology 9, 249–263 (1970)

    Google Scholar 

  • Sulser, F., Owens, M., Norvich, M., Dingell, J.: The relative role of storage and synthesis of brain norepinephrine in the psychomotor stimulation evoked by amphetamine or by desipramine and tetrabenazine. Psychopharmacologia (Berl.) 12, 322–332 (1968)

    Google Scholar 

  • Thierry, A. M., Javoy, F., Glowinski, J., Kety, S. S.: Effects of stress on the metabolism of norepinephrine, dopamine, and serotonin in the central nervous system of the rat: I. Modification of norepinephrine turnover. J. Pharmacol. exp. Ther. 163, 163–171 (1968)

    Google Scholar 

  • Thoa, N. B., Eichelman, B., Richardson, J., Jacobowitz, D.: 6-hydroxydopa depletion of brain norepinephrine and the facilitation of aggressive behavior. Science 178, 75–77 (1972)

    Google Scholar 

  • Ungerstedt, U.: Postsynaptic supersensitivity after 6-hydroxydopamine induced degeneration of the nigro-striatal dopamine system. Acta physiol. scand., Suppl. 367, 69–93 (1971 a)

    Google Scholar 

  • Ungerstedt, U.: Histochemical studies on the effect of intracerebral and intraventricular injections of 6-hydroxy-dopamine on monoamine neurons in the rat brain. In: T. Malmfors and H. Thoenen (Eds.): Proceedings of the 6-Hydroxy-Dopamine Symposium, pp. 101–127. Amsterdam: North Holland Publ. 1971 b

    Google Scholar 

  • Uretsky, N. J., Iversen, L. L.: Effects of 6-hydroxydopamine on catecholamine containing neurones in the rat brain. J. Neurochem. 17, 269–278 (1970)

    Google Scholar 

  • Uretsky, N. J., Simmonds, M. A., Iversen, L. L.: Changes in the retention and metabolism of 3H-L-norepinephrine in rat brains in vivo after 6-hydroxy-dopamine pretreatment. J. Pharmacol. exp. Ther. 176, 489–496 (1971)

    Google Scholar 

  • Valzelli, L.: Drugs and aggressiveness. Advanc. Pharmacol. 5, 79–108 (1967)

    Google Scholar 

  • Weiss, J. M., Stone, E. A., Harrell, N.: Coping behavior and brain norepinephrine. J. comp. physiol. Psychol. 72, 153–160 (1970)

    Google Scholar 

  • Weissman, A., Koe, K. and Tenen, S.: Amphetamine effects following inhibition of tyrosine hydroxylase. J. pharmacol. exp. Ther. 151, 339–352 (1965)

    Google Scholar 

  • Wender, P. H.: The minimal brain dysfunction syndrome in children. J. nerv. ment. Dis. 155, 55–71 (1972)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

These data were part of Ph. D. dissertation by C.A.S. submitted to the Department of Psychology, U.C.L.A.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sorenson, C.A., Ellison, G.D. Nonlinear changes in activity and emotional reactivity scores following central noradrenergic lesions in rats. Psychopharmacologia 32, 313–325 (1973). https://doi.org/10.1007/BF00429467

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00429467

Key words

Navigation