Advertisement

Molecular and Chemical Neuropathology

, Volume 30, Issue 3, pp 213–222 | Cite as

Morphochemical changes in brain structures in the course of chronic haloperidol treatment and the correction of these changes with tuftsin

  • L. M. Gershtein
  • M. T. Dobrynina
  • A. V. Sergutina
Original Articles

Abstract

The systemic injection of haloperidol (4 wk, 0.5 mg/kg/d) caused the increase of protein concentration and content, and the activity level of aminopeptidase in the cytoplasm of the neurons of associated type (layer III). The nucleus of these cells decreased both in sizes and in the content of proteins. In the neurons of efferent-projectory type (alyer V), the decrease of studied peculiarities as compared with control level was observed. Tuftsin (300 μg/kg/d) injection after chronic haloperidol treatment causes the restoring action on changed parameters in sensomotor cortex. In caudate nucleus, tuftsin influence caused further reduction of neuron's cytoplasmic area and significant reduction in protein content.

The received results testify to the morphobiochemical heterogenity of investigated brain structures, which is displayed both in the case of haloperidol treatment and in the case of its correction by neuropeptide tuftsin.

Chronic haloperidol administration to animals can develop a model of certain symptoms and syndromes of parkinsonism. Its most pronounced manifestation is an imbalance in the neuromediator systems, especially the dopaminergic one (Mettler and Crandall, 1959; Colls, 1984; Funk et al., 1986).

The research was performed in conjunction with the physiologists, whose experiments have shown that after chronic haloperidol administration, changes in animal behavior are developed that are typical for bradikinesia, and the motor regimen of integration is disturbed (Popova and Kachalova, 1991; Dovedova and Povova, 1993). Regulatory drugs, especially the tetrapeptide tuftsin, seem to correct such disturbances.

Index Entries

Sensorimotor cortex caudate nucleus protein metabolism haloperidol tuftsin interferometry aminopeptidase 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Adrianov O. S., Molodkina L. N., and Yamshchikova N. G. (1987) Association systems of the brain and extrapolation behavior. USSR Academy of Medical Sciences, Moscow, Medicine, p. 192.Google Scholar
  2. Andreev S. M., Vanohin K. V., Antonova L. V., and Ashmarin I. P. (1980) Tetrapeptid tuftsin influence to the emotional behaviour of animals.DAS USSR 253,2, 498–500.Google Scholar
  3. Colls A. R. (1984) Basal ganglia and Parkinson's disease: neurobiological and pharmacological aspects in animals and man.Clin. Neurol. Neurosurg. 86,3, 178–195.CrossRefGoogle Scholar
  4. Dovedova Ye. L. and Popova N. S. (1993) Pathogenetic mechanisms of drug parkinsonism: biochemical and bioelectric evaluation of haloperidol effects in experiment.S.S. Korsakov J. Neurol. Psychiatry 93,6, 15–18.Google Scholar
  5. Fridkin M. and Gottlieb P. (1981) Tuftsin, Thr-Lys-Pro-Agr.Mol. Cell. Biochem. 41, 73–97.PubMedCrossRefGoogle Scholar
  6. Funk K. F., Schmidt Z., and Westerman K. H. (1986) Zur Frage der biochemischen Charakterisierung und Differenzierung der dophaminergen Supersensititat bei der Ratte.Biomed. Biochim. Acta 45,3, 393–399.PubMedGoogle Scholar
  7. Gershtein L. M. (1965) Histochemical method for the determination of aminopeptidase in the nervous tissue.J. Cytol. 6, 769–773.Google Scholar
  8. Gershtein L. M., Dovedova E. L., Kamysheva A. C., Sergutina A. V., and Chebotareva T. L. (1990) Effect of tuftsin on some patterns of metabolism in animal brain locomotory system.Voprosi Med. Chim. 4, 15–17.Google Scholar
  9. Kamensky A. A., Kalikhevich V. N., and Sarycheva N. Yu. (1986) Time course of behavioral tuftsin effect.Bull. Exp. Biol. Med. 101,1, 55–57.Google Scholar
  10. Kazakova P. V. and Nezlina N. I. (1972) Changes in evoked potentials and neuronal dry mass of cat motor cortex neurons in the process of compensatory reorganization.J. Neurophysiol. 4,1, 41–47.Google Scholar
  11. Konkoy C. S., Oakes M. G., and Davis T. P. (1993) Chronic treatment with neuroleptics alters neutral endopeptidase 24.11 activity in rat brain regions.Peptides 14, 1017–1020.PubMedCrossRefGoogle Scholar
  12. Matz V. N., Segal O. L., and Kruglikov R. I. (1987) Change in the dry weight of neurons of motor cortex in rats at unlocal alimentary instrumental reflex elaboration in normal conditions and at the background of iproniasid action.Proc. USSR Acad. Sci. Ser. Biol. 3, 430–437.Google Scholar
  13. Mettler F. A. and Crandall A. (1959) Relation between parkinsonism and psychiatric disorder.J. Nervous Mental Dis. 129,1, 551–559.Google Scholar
  14. Najjar V. A. and Nishioka K. (1970) Tuftsin, a physiological phagocytosis-stimulating peptide.Nature 228, 672,673.PubMedCrossRefGoogle Scholar
  15. Nishioka K., Constantopoulus A., Saton P. S., Mitchell W., and Najjar V. A. (1973) Characteristics and isolation of the phagocytosis—stimulating peptide, tuftsin.Biochim. Biophys. Acta 310, 217–229.PubMedGoogle Scholar
  16. Nishioka K., Babcock G. E., Phillips J. N., and Noyes R. D. (1981) Anti-tumor effect of tuftsin.Mol. Cell. Biochem. 41, 13–18.PubMedCrossRefGoogle Scholar
  17. Pehek E. A. and Yamamoto B. K. (1994) Differential effects of locally administered clozapine and haloperidol on dopamine efflux in the rat prefrontal cortex and caudate-putamen.J. Neurochem. 63, 2118–2124.PubMedCrossRefGoogle Scholar
  18. Popova N. S. and Kachalova L. M. (1991) Principles of intercentral interaction variants of disturbances and ways of reconstruction. Jurnal vyschei nervnoi deyatelnosty.J. Higher Nervous Activity 41,1, 9–32.Google Scholar
  19. Valdman A. V. (1981) Neuropeptides and emotional behaviour.Adv. Pharmacol. Ther. Por. Int. Congr. 8th (Pub. 1982),1, 165–173.Google Scholar
  20. Yoshida Y., Ono T., Kowano K., and Miyagishi T. (1994) Distinct sites of dopaminergic and glutamatergic regulation of haloperidol-induced catalepsy within the rat caudate-putamen.Brain Res. 639, 139–148.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc 1997

Authors and Affiliations

  • L. M. Gershtein
    • 1
  • M. T. Dobrynina
    • 1
  • A. V. Sergutina
    • 1
  1. 1.Brain Research Institute of RAMSMoscowRussia

Personalised recommendations