Summary
The regional prevention by neuroleptic drugs of specificin vivo 3H-spiperone binding was studied in the rat brain. L-sulpiride, thioridazine and clozapine were found to reduce the3H-spiperone binding selectively in the olfactory tubercle, septum, substantia nigra region and frontal cortex but not the striatum at dose levels which preferentially block apomorphine (APO) induced hyperactivity. The maximal prevention of specific3H-spiperone binding by l-sulpiride and clozapine reached 60–80% in the former structures while the displacement of striatal3H-spiperone binding did not exceed 40%. In contrast to l-sulpiride, thioridazine and clozapine both chlorpromazine and haloperidol reduced the3H-spiperone binding to the same extent in all regions studied. Chlorpromazine and haloperidol were potent in prevention of striatal3H-spiperone bindingin vivo which reached 60–80% in this structure.
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References
Andén, N.-E., Stock, G.: Effect of clozapine on the turnover of dopamine in the corpus striatum and the limbic system. J. Pharm. Pharmacol.25, 346–348 (1973).
Bartholini, G.: Differential effects of neuroleptic drugs on dopamine turnover in the extrapyramidal and limbic system. J. Pharm. Pharmacol.28, 429–433 (1976).
Baudry, M., Martres, M. P., Schwartz, J. C.: In vivo binding of3H-pimozide in mouse striatum: effects of dopamine agonists and antagonists. Life Sci.21, 1163–1170 (1977).
Bischoff, S., Bittiger, H., Krauss, J.:In vivo 3H-spiperone binding to the rat hippocampal formation: involvement of DA receptors. Europ. J. Pharmacol.58, 305–315 (1980).
Carlsson, A.: Does Dopamine have a role in schizophrenia? Biol. Psychiat.13, 3–21 (1978).
Cools, E. R., Honig, W. M. M., Pijneburg, A. J. J., Van Rossum, J. M.: The nucleus accumbens of rats and dopaminergic mechanisms regulating locomotor behaviour. Neurosci. Lett.3, 335 (1976).
Costall, B., Naylor, R. J.: The roles of telencephalic dopaminergic systems in the mediation of apomorphine-stereotyped behaviour. Europ. J. Pharmacol.24, 8–24 (1973).
Costall, B., Naylor, R. J.: The behavioural effects of dopamine applied intracerebrally to areas of the meso-limbic system. Europ. J. Pharmacol.32, 87–92 (1975).
Costall, B., Marsden, C. D., Naylor, R. J., Pycock, C. J.: Stereotyped behaviour patterns and hyperactivity induced by amphetamine and ampomorphine after discrete 6-hydroxydopamine lesions of extrapyramidal and meso-limbic nuclei. Brain Res.123, 89–111 (1977).
Creese, I., Snyder, S. H.:3H-spiroperidole labels serotonin receptors in rat cerebral cortex and hippocampus. Europ. J. Pharmacol.49, 201–203 (1978).
Crow, T. J., Deakin, J. F. W., Longden, A.: The nucleus accumbens, possibly site of antipsychotic action of neuroleptic drugs. Psychol. Med.7, 213–221 (1977).
Fuxe, K., Ögren, S.-O., Fredholm, B., Agnati, L., Hökfelt, T., Perez de la Mora, M.: Possibilities of a differential blockade of central monoamine receptors. In: Rhinencephale Neurotransmitteurs et Psychoses (de Ajuriaguerra, J., Tissot, R., eds.), Symposium Bel-Air V, pp. 253–289. Geneva: Georg & Cie. 1977.
Jenner, P., Marsden, C. D.: The substituted benzamides-a novel class of dopamine antagonists. Life Sci.25, 479–486 (1979).
Jenner, P., Elliot, P. N. C., Clow, A., Reavill, C., Marsden, C. D.: A comparison ofin vitro andin vivo dopamine antagonism produced by substituted benzamide drugs. J. Pharm. Pharmacol.31, 46–48 (1978).
Jenner, P., Clow, A., Reavill, C., Theodorou, A., Marsden, C. D.: Stereoselective actions of substituted benzamide drugs on cerebral dopamine mechanisms. J. Pharm. Pharmacol.32, 39–44 (1980).
Kebabian, J. W., Calne, D. B.: Multiple receptors for dopamine. Nature277, 93–96 (1979).
Kelly, P. H., Seviour, P. W., Iversen, S. D.: Amphetamine and apomorphine responses in the rat following 6-OHDA lesions of the nucleus accumbens septi and corpus striatum. Brain Res.94, 507–522 (1975).
Köhler, Ch., Ögren, S.-O., Haglund, L., Ängeby, T.: Regional displacement by sulpiride of3H-spiperone bindingin vivo. Biochemical and behavioural evidence for a preferential action on limbic and nigral dopamine receptors. Neurosci. Lett.13, 51–56 (1979).
Köhler, Ch., Fuxe, K., Ross, S. B.: Regionalin vivo binding of (3H) N-propylnorapomorphine in the mouse brain. Evidence for labelling of central dopamine receptors. Europ. J. Pharmacol. (in press, 1981).
Kuhar, M. J., Murrin, C. L., Malouf, A. T., Klemm, N.: Dopamine receptor bindingin vivo, the feasibility of autoradiographic studies. Life Sci.22, 203–210 (1978).
Laduron, P., Leysen, J.: Specificin vivo binding of neuroleptic drugs in rat brain. Biochem. Pharmacol.26, 1003–1007 (1977).
Le Fur, G., Guilloux, F., Uzan, A.:In vivo blockade of dopaminergic receptors from different rat brain regions by classical and atypical neuroleptics. Biochem. Pharmacol.29, 267–270 (1980).
Leysen, J. E., Niemegeers, C. J. E., Tollenaere, J. P., Laduron, P.: Serotoninergic component of neuroleptic receptors. Nature (Lond.)272, 168–171 (1978).
Ljungberg, T., Ungerstedt, U.: Classification of neuroleptic drugs according to their ability to inhibit apomorphine induced locomotion and gnawing: evidence for two different mechanisms of action. Psychopharmacology56, 239–247 (1978).
Ögren, S.-O., Hall, H., Köhler, Ch.: Studies on the stereoselective dopamine receptor blockade in the rat brain by rigid spiroamines. Life Sci.23, 1769–1774 (1978).
Ögren, S.-O., Fuxe, K., Agnati, L. F., Gustavsson, J. Å., Jonsson, G., Holm, A. C.: Reevaluation of the indoleamine hypothesis of depression. Evidence for a reduction of functional activity of central 5-HT systems by antidepressant drugs. J. Neural Transm.46, 85–103 (1979).
Scatton,B., Worms,P., Zivkovic,B., Deportere,H., Dedek,J., Bartholini,G.: On the neuropharmacological spectra of “classical” (haloperidole) and “atypical” (benzamide derivatives) neuroleptics. In: Sulpiride and other benzamides (Spano, P. F., Trabucci, M., Corsini, G. U., Gessa, G. L., eds.), pp. 53–66. 1979.
Waldmeier, P. C., Maitre, L.: On the relevance of preferential increases of mesolimbic versus striatal dopamine turnover for the prediction of antipsychotic drugs. J. Neurochem.27, 589–597 (1976).
Westerink, B. H. C., Lejeuene, B., Korf, J., van Praag, H. M.: On the significance of regional dopamine metabolism in the rat brain for the classification of centrally acting drugs. Europ. J. Pharmacol.42, 179–190 (1977).
Weisel, F. A., Sedvall, G.: Effects of antipsychotic drugs on homovanillic acid levels in the striatum and the olfactory tubercle of the rat. Europ. J. Pharmacol.30, 364–367 (1975).
Wilk, S., Glick, S. D.: Dopamine metabolism in the nucleus accumbens: the effect of clozapine. Europ. J. Pharmacol.37, 203–206 (1976).
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Köhler, C., Haglund, L., Ögren, S.O. et al. Regional blockade by neuroleptic drugs ofin vivo 3H-spiperone binding in the rat brain. Relation to blockade of apomorphine induced hyperactivity and stereotypies. J. Neural Transmission 52, 163–173 (1981). https://doi.org/10.1007/BF01249601
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DOI: https://doi.org/10.1007/BF01249601