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Antagonism of apomorphine- and d-amphetamine-induced stereotyped behaviour by injection of low doses of haloperidol into the caudate nucleus and the nucleus accumbens

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Abstract

The effects of intracerebral injections of the dopa-mine-antagonist haloperidol upon stereotyped behaviour, induced by peripheral administration of apomorphine and d-amphetamine in rats, were investigated. A system was used by which injections into the brain could be performed during the stereotyped behaviour without disturbing the animals. Administration of low doses of haloperidol (2.5 and 5 Μg) bilaterally either into the caudate nucleus or into the nucleus accumbens resulted in a dose-dependent antagonism of stereotyped behaviour. Whereas the effect of haloperidol upon stereotyped behaviour, induced by apomorphine, consisted mainly in a shortening of the duration of action, more abnormal behavioural patterns were seen, when haloperidol was administered to animals, who had received d-amphetamine. No clear differences were found between injections into the caudate nucleus and injections into the nucleus accumbens.

Neither administration of the local anesthetic agent procaine into the caudate nucleus nor into the nucleus accumbens did significantly reduce apomorphine-induced stereotyped behaviour. The possible way in which haloperidol, following central administration, influences stereotyped behaviour is discussed.

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References

  1. Andén, N.-E., Butcher, S. G., Corrodi, H., Fuxe, K., Ungerstedt, U.: Receptor activity and turnover of dopamine and noradrenaline after neuroleptics. Europ. J. Pharmacol. 11, 303–314 (1970)

  2. Andén, N.-E., Fuxe, K., Hamberger, B., Hökfelt, T.: A quantitative study on the nigro-neostriatal dopamine neuron system in the rat. Acta physiol. scand. 67, 306–312 (1966)

  3. Andén, N.-E., Rubenson, A., Fuxe, K., Hökfelt, T.: Evidence for dopamine receptor stimulation by apomorphine. J. Pharm. Pharmacol. 19, 627–629 (1967)

  4. Asher, I. M., Aghajanian, G. K.: 6-Hydroxydopamine lesions of olfactory tubercles and caudate nuclei: effect on amphetamine-induced stereotyped behavior in rats. Brain Res. 82, 1–12 (1974)

  5. Bertler, å., Rosengren, E.: Occurrence and distribution of dopamine in brain and other tissues. Experientia (Basel) 15, 10–11 (1959)

  6. Butcher, L. L., Eastgate, S. M., Hodge, G. K.: Evidence that punctate intracerebral administration of 6-hydroxydopamine fails to produce selective neuronal degeneration. Naunyn-Schmiedeberg's Arch. Pharmacol. 285, 31–70 (1974)

  7. Costall, B., Naylor, R. J.: On the mode of action of apomorphine. Europ. J. Pharmacol. 21, 350–361 (1973a)

  8. Costall, B., Naylor, R. J.: The role of telencephalic dopaminergic systems in the mediation of apomorphine-stereotyped behaviour. Europ. J. Pharmacol. 24, 8–24 (1973b)

  9. Costall, B., Naylor, R. J.: The involvement of dopaminergic systems with the stereotyped behaviour patterns induced by methylphenidate. J. Pharm. Pharmacol. 26, 30–33 (1974a)

  10. Costall, B., Naylor, R. J.: Extrapyramidal and mesolimbic involvement with the Stereotypic activity of d- and l-amphetamine. Europ. J. Pharmacol. 25, 121–129 (1974b)

  11. Costall, B., Naylor, R. J., Olley, J. E.: Stereotypic and anticataleptic activities of amphetamine after intracerebral injections. Europ. J. Pharmacol. 18, 83–94 (1972a)

  12. Costall, B., Naylor, R. J., Olley, J. E.: The substantia nigra and stereotyped behaviour. Europ. J. Pharmacol. 18, 95–106 (1972b)

  13. Creese, I., Iversen, S. D.: The role of forebrain dopamine systems in amphetamine induced stereotyped behavior in the rat. Psychopharmacologia (Berl.) 39, 345–357 (1974)

  14. Divac, I.: Drug-induced syndromes in rats with large chronic lesions in the corpus striatum. Psychopharmacologia (Berl.) 27, 171–178 (1972)

  15. Ernst, A. M.: Mode of action of apomorphine and dexamphetamine on gnawing compulsion in rats. Psychopharmacologia (Berl.) 10, 316–323 (1967)

  16. Ernst, A. M., Smelik, P. G.: Site of action of dopamine and apomorphine on compulsive gnawing behavior in rats. Experientia (Basel) 22, 837–838 (1966)

  17. Fog, R.: Stereotyped and non-stereotyped behaviour in rats induced by various stimulant drugs. Psychopharmacologia (Berl.) 14, 299–304 (1969)

  18. Fog, R., Pakkenberg, H.: Behavioral effects of dopamine and p-hydroxyamphetamine injected into corpus striatum of rats. Exp. Neurol. 31, 75–86 (1971)

  19. Fog, R., Randrup, A., Pakkenberg, H.: Lesions in corpus striatum and cortex of rat brains and the effect on pharmacologically induced stereotyped aggressive and cataleptic behaviour. Psychopharmacologia (Berl.) 18, 346–356 (1970)

  20. Fog, R., Randrup, A., Pakkenberg, H.: Intrastriatal injections of quaternary butyrophenones and oxypertine: neuroleptic effects in rats. Psychopharmacologia (Berl.) 19, 224–230 (1971)

  21. Fuxe, K., Ungerstedt, U.: Histochemical, biochemical and functional studies on central monoamine neurons after acute and chronic amphetamine administration. In: Amphetamines and related compounds. E. Costa and S. Garattini, eds., pp. 257–288. New York: Raven Press 1970

  22. Janssen, P. A. J., Niemegeers, C. J. E., Jageneau, A. H. M.: Apomorphine-antagonism in rats. Arzneimittel-Forsch. 10, 1003–1005 (1960)

  23. Janssen, P. A. J., Niemegeers, C. J. E., Schellekens, K. H. L., Lenaerts, F. M.: Is it possible to predict the clinical effects of neuroleptic drugs (major tranquillizers) from animal data? (Part IV). Arzneimittel-Forsch. 17, 841–854 (1967)

  24. König, J. F. R., Klippel, R. A.: The rat brain. Baltimore: Williams and Wilkins 1963

  25. McKenzie, G. M.: Role of the tuberculum olfactorium in stereotyped behaviour induced by apomorphine in the rat. Psychopharmacologia (Berl.) 23, 212–219 (1972)

  26. Naylor, R. J., Olley, J. E.: Modification of the behavioural changes induced by amphetamine in the rat by lesions in the caudate nucleus, the caudate-putamen and globus pallidus. Neuropharmacology 11, 91–99 (1972)

  27. Poirier, L. J., Langelier, P., Roberge, A., Boucher, R., Kitsikis, A.: Non-specific histopathological changes induced by intracerebral injection of 6-hydroxydopamine. J. neurol. Sci. 16, 401–416 (1972)

  28. Pijnenburg, A. J. J., Honig, W. M. M., van Rossum, J. M.: Inhibition of d-amphetamine-induced locomotor activity by injection of haloperidol into the nucleus accumbens of the rat. Psychopharmacologia (Berl.) 41, 87–95 (1975)

  29. Randrup, A., Munkvad, I.: On the role of catechol amines in the amphetamine excitatory response. Nature (Lond.) 211, 540 (1966)

  30. Randrup, A., Munkvad, I.: Stereotyped activities produced by amphetamine in several animal species and man. Psychopharmacologia (Berl.) 11, 300–310 (1967)

  31. Randrup, A., Munkvad, I.: Biochemical, anatomical and psychological investigations of stereotyped behavior induced by amphetamines. In: Amphetamines and related compounds. E. Costa and S. Garattini, eds., pp. 695–713. New York: Raven Press 1970

  32. Roos, B.-E.: Decrease in homovanillic acid as evidence for dopamine receptor stimulation by apomorphine in the neostriatum of the rat. J. Pharm. Pharmacol. 21, 263–264 (1969)

  33. Rossum, J. M. van: The significance of dopamine receptor blockade for the mechanism of action of neuroleptic drags. Arch. int. Pharmacodyn. 160, 492–494 (1966)

  34. Rossum, J. M. van: Mode of action of psychomotor stimulant drugs. Int. Rev. Neurobiol. 12, 307–383 (1970)

  35. Seeman, P.: The membrane actions of anesthetics and tranquillizers. Pharmacol. Rev. 24, 583–655 (1972)

  36. Seeman, P., Staiman, A., Chau-Wong, M.: The nerve impulse-blocking actions of tranquillizers and the binding of neuroleptics to synaptosome membranes. J. Pharmacol. exp. Ther. 190, 123–130 (1974)

  37. Ungerstedt, U.: Stereotaxic mapping of the monoamine pathways in the rat brain. Acta physiol. scand. 82, Suppl. 367, 1–48 (1971)

  38. Weissman, A., Koe, B. K., Tenen, S. S.: Antiamphetamine effects following inhibition of tyrosine hydroxylase. J. Pharmacol. exp. Ther. 151, 339–352 (1966)

  39. Wolfarth, S.: Reactions to apomorphine and spiroperidol of rats with striatal lesions: the relevance of kind and size of the lesion. Pharmacol. Biochem. Behav. 2, 181–186 (1974)

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Pijnenburg, A.J.J., Honig, W.M.M. & Van Rossum, J.M. Antagonism of apomorphine- and d-amphetamine-induced stereotyped behaviour by injection of low doses of haloperidol into the caudate nucleus and the nucleus accumbens. Psychopharmacologia 45, 65–71 (1975). https://doi.org/10.1007/BF00426211

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Key words

  • Haloperidol
  • Apomorphine
  • d-Amphetamme
  • Procaine
  • Caudate nucleus
  • Nucleus accumbens
  • Stereotyped behaviour