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Long-term effect of perphenazine on the substantia nigra in rats

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Abstract

A controlled blind study was made of the long-term effect of perphenazine enanthate (3.4 mg/kg/14 days for 12 months and 40 mg/kg/14 days for 6 months) upon the number of nerve cells (light microscopy) and the uptake of 3H-uridine (autoradiography) in the substantia nigra of rats. No significant differences were found between the numbers of nerve cells in treated and untreated animals, neither in the pars compacta nor in the pars reticularis. Nor were any significant differences found with regard to cell cytology or uptake of 3H-uridine. On the basis of the present data and certain clinical and neuroanatomic studies of patients with persistent signs of encephalopathy following long-term neuroleptic treatment it is suggested that perphenazine and related neuroleptics may exert an irreversible neurotoxic effect on the cells in the nigro-striatal system, but that this effect is not manifest until an elevated sensitivity to neuroleptics is present, e.g. in the form of age phenomena and/or psychiatric disease processes.

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References

  • Abercrombie, M.: Estimation of nuclear population from microtome sections. Anat. Rec. 94, 239–247 (1946)

    Google Scholar 

  • Aghajanian, G. K., Bunney, B. S.: Dopaminergic and non-dopaminergic neurons of the substantia nigra: Differential responses to putative transmitters. J. Pharmacol. (Paris) 5, Suppl. 1, 56–57 (1974)

    Google Scholar 

  • Ayd, F. J.: Persistent dyskinesia: a neurological complication of major tranquillizers. Med. Sci. 18, 32–40 (1967)

    Google Scholar 

  • Barbeau, A.: l-Dopa therapy in Parkinson's disease: A critical review of nine years' experience. Canad. med. Ass. J. 101, 59–68 (1969)

    Google Scholar 

  • Bernheimer, H., Birkmayer, W., Hornykiewicz, O., Jellinger, K., Seitelberger, F.: Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations. J. neurol. Sci. 20, 415–455 (1973)

    Google Scholar 

  • Carpenter, M. B., Peter, P.: Nigrothalamic and nigrostriatal fibers in the Rhesus monkey. J. comp. Neurol. 144, 93–116 (1972)

    Google Scholar 

  • Christensen, E., MØller, J. E., Faurbye, A.: Neuropathological investigations of 28 brains from patients with dyskinesia. Acta psychiat. scand. 46, 14–23 (1970)

    Google Scholar 

  • Crane, G. E.: Tardive dyskinesia in patients treated with major neuroleptics: A review of the literature. Amer. J. Psychiat. 124, 40–48 (1968)

    Google Scholar 

  • Crane, G. E.: Pseudoparkinsonism and tardive dyskinesia. Arch. Neurol. (Chic.) 27, 426–430 (1972)

    Google Scholar 

  • Crane, G. E.: Persistent dyskinesia. Brit. J. Psychiat. 122, 395–405 (1973)

    Google Scholar 

  • Crane, G. E.: Risk of long-term therapy with neuroleptic drugs. Symposium on Antipsychotic Drugs, Pharmacodynamics and Pharmacokinetics, G. Sedvall, B. UvnÄs and Y. Zotterman (ededs.). Oxford: Pergamon Press (in press)

  • Edwards, H.: The significance of brain damage in persistent oral dyskinesia. Brit. J. Psychiat. 116, 271–275 (1970)

    Google Scholar 

  • Farm, W., Lake, R.: On the coexistence of Parkinsonism and tardive dyskinesia. Dis. nerv. Syst. 35, 324–326 (1974)

    Google Scholar 

  • Faull, R., Carman, J.: Ascending projections of the substantia nigra in the rat. J. comp. Neurol. 132, 73–92 (1968)

    Google Scholar 

  • Faull, R., Laverty, R.: Changes in dopamine levels in the corpus striatum following lesions in the substantia nigra. Exp. Neurol. 23, 332–340 (1969)

    Google Scholar 

  • Finch, C.: Catecholamine metabolism in the brains of ageing male mice. Brain Res. 52, 261–276 (1973)

    Google Scholar 

  • Fog, R., Pakkenberg, H., Juul, P., Bock, E., Andersen, J.: High dose treatment of rat with perphenazine enanthate (in preparation)

  • Gerlach, J.: Relation between paralysis agitans, l-Dopa-induced hyperkinesia and tardive dyskinesia-(in preparation)

  • Gerlach, J., Reisby, N., Randrup, A.: Dopaminergic hypersensitivity and cholinergic hypofunction in the pathophysiology of tardive dyskinesia. Psychopharmacologia (Berl.) 34, 21–35 (1974)

    Google Scholar 

  • Gerlach, J., Thorsen, K.: The movement pattern of oral tardive dyskinesia in relation to anticholinergic and antidopaminergic treatment. Int. Pharmacopsychiat (in press)

  • Gross, H., KaltenbÄck, E.: Neuropathological findings in persistent hyperkinesia after neuroleptic long-term therapy. In: The present status of psychotropic drugs, A. Cerletti and F. J. Bové, eds., pp. 474–476. Amsterdam: Excerpta Medica Foundation 1968

    Google Scholar 

  • Gulley, R., Wood, R.: The fine structure of the neurons in the rat substantia nigra. Tissue & Cell 3, 675–690 (1971)

    Google Scholar 

  • Hassler, R.: Zur Pathologie der Paralysis agitans und des postenzephalitischen Parkinsonismus. J. Psychol. Neurol. (Lpz.) 48, 387–476 (1938)

    Google Scholar 

  • Hassler, R.: Extra-pyramidal-motorische Syndrome und Erkrankungen. In: Handbuch der inneren Medizin, vol. 4, G. v. Bergmann, W. Frey, H. Schwiegk and R. Jung, eds., pp. 676–904. Berlin-Göttingen-Heidelberg: Springer 1955

    Google Scholar 

  • Hedgreen, J.: Separate demonstration of dopaminergic and non-dopaminergic projections of substantia nigra in the rat. Anat. Rec. 169, 338 (1971)

    Google Scholar 

  • Hershon, H., Kennedy, P., Mc Guire, R.: Persistence of extra-pyramidal disorders and psychiatric relapse after withdrawal of long-term phenothiazine therapy. Brit. J. Psychiat. 120, 41–50 (1972)

    Google Scholar 

  • Hökfelt, T., Ungerstedt, U.: Electron and fluorescence microscopical studies on the nucleus caudatus putamen of the rat after unilateral lesions of ascending nigro-neostriatal dopamine neurons. Acta physiol. scand. 76, 415–426 (1969)

    Google Scholar 

  • Kiloh, L., Smith, J., Williams, S.: Antiparkinson drugs as causal agents in tardive dyskinesia. Med. J. Austr. 1973, 591–593

  • Klawans, H.: The pharmacology of tardive dyskinesia. Amer. J. Psychiat. 130, 82–86 (1973)

    Google Scholar 

  • Klawans, H., Rubovits, R.: Effect of cholinergic and anticholinergic agents on tardive dyskinesia. J. Neurol. Neurosurg. Psychiat. 27, 941–947 (1974)

    Google Scholar 

  • König, J., Klippel, R.: Stereotaxic atlas of rat brain. Baltimore: The Williams and Wilkins Comp. 1963

    Google Scholar 

  • Pakkenberg, H., Fog, R., Nilakantan, B.: The long-term effect of perphenazine enanthate on the rat brain. Psychopharmacologia (Berl.) 29, 329–336 (1973)

    Google Scholar 

  • Roizin, L., True, C., Knight, M.: Structural effects of tranquillizers. Ass. Res. nerv. ment. Dis. Proc. 37, 285–324 (1959)

    Google Scholar 

  • Ungerstedt, U.: Post-synaptic supersensitivity after 6-hydroxy-dopamine induced degeneration of the nigro-striatal dopamine system. Acta physiol. scand., Suppl. 367, 69–73 (1971)

    Google Scholar 

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Gerlach, J. Long-term effect of perphenazine on the substantia nigra in rats. Psychopharmacologia 45, 51–54 (1975). https://doi.org/10.1007/BF00426209

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