Summary
Intra-accumbens injection of sulpiride, tiapride, and metoclopramide antagonized locomotor hyperactivity induced by intraperitoneal administration of apomorphine in rats and measured over the first five minutes after introducing the animal to an open-field cage. Sulpiride was slightly more potent than tiapride which was more than 10 times more potent than metoclopramide and haloperidol. The threshold dose of sulpiride was as low as 0.001μg, bilaterally. Intra-accumbens injection of sulpiride also blocked exploratory hypermotility induced by bilateral intra-accumbens injections of apomorphine and picrotoxin. The threshold dose of sulpiride for blocking these two effects was about 0.01μg, bilaterally. Sulpiride was more than 10 times more potent than haloperidol in blocking this apomorphine-induced hypermotility. Haloperidol did not influence the picrotoxin hypermotility.
The results obtained indicate strong postsynaptic dopamine antagonist properties of sulpiride, tiapride and metoclopramide.
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Aghajanian, G. K., Bunney, B. S.: Central dopaminergic neurons: neurophysiological identification and responses to drugs. In: Frontiers in Catecholamine Research (Usdin, E., Snyder, S. H., eds.), pp. 643–648. New York: Pergamon Press. 1973.
Arnt, J.: Neuroleptic inhibition of 6, 7-ADTN-induced hyperactivity after injection into the nucleus accumbens, specifity and comparison with other models. Eur. J. Pharmacol.90, 47–55 (1983).
Costall, B., Eniojukan, J. F., Naylor, R. J.: Spontaneous climbing behavior of mice, its measurement and dopaminergic involvement. Eur. J. Pharmacol.85, 125–132 (1982).
Costall, B., Fortune, D. H., Naylor, R. J.: Differential activities of some benzamide derivatives on peripheral and intracerebral administration. J. Pharm. Pharmacol.30, 796–798 (1978).
Costall, B., Hui, S.-C. G., Naylor, R. J.: Differential actions of substituted benzamides on pre- and postsynaptic dopamine receptor mechanisms in the nucleus accumbens. J. Pharm. Pharmacol.32, 594–596 (1980).
Costall, B., Lim, S. K., Naylor, R. J.: Characterization of the mechanisms by which purported dopamine agonists reduce spontaneous locomotor activity of mice. Eur. J. Pharmacol.73, 175–188 (1981).
Honda, F. Y., Satoh, Y., Shimomura, K., Satoh, H., Noguchi, H., Uchida, S., Kato, R.: Dopamine receptor blocking activity of sulpiride in the central nervous system. Jap. J. Pharmacol.27, 397–411 (1977).
Kendler, K. S., Bracha, H. S., Davis, K. L.: Dopamine autoreceptor and postsynaptic receptor blocking potency of neuroleptics. Eur. J. Pharmacol.79, 217–223 (1982).
König, J. F. R., Klippel, R. A.: The Rat Brain. A Stereotactic Atlas of the Forebrain and Lower Parts of the Brain Stem. Baltimore: Williams and Wilkins. 1963.
Morgenstern, R., Fink, H.: Sulpiride potentiates locomotor hyperactivity-a consequence of serotonergic-dopaminergic interaction? Biogenic Amines2 (in press, 1985).
Morgenstern, R., Fink, H., Oelssner, W.: LSD-potentiated apomorphine hypermotility: a model for differentiating antipsychotic drugs. Pharmacol. Biochem. Behav.18, 13–17 (1983 a).
Morgenstern, R., Gold, R., Oelssner, W.: Lokomotorische Aktivität und Nucleus accumbens. Biomed. Biochim. Acta42, 947–953 (1983 b).
Morgenstern, R., Mende, T., Gold, R., Lemme, P., Oelssner, W.: Drug-induced modulation of locomotor hyperactivity induced by picrotoxin in nucleus accumbens. Pharmacol. Biochem. Behav.21, 501–506 (1984).
Nishibe, Y., Matsuo, Y., Yoshizaki, T., Eigyo, M., Shiomi, T., Hirose, K.: Differential effects of sulpiride and metoclopramide on brain. Homovanillic acid levels and shuttle box avoidance after systemic and intracerebral administration. Naunyn-Schmiedeberg's Arch. Pharmacol.321, 190–194 (1982).
O'Connor, S. E., Brown, R. A.: The pharmacology of sulpiride-a dopamine receptor antagonist. Gen. Pharmacol.13, 185–193 (1982).
Pinnock, R. D., Woodruff, G. N., Turnbull, M. J.: Sulpiride blocks the action of dopamine in the rat substantia nigra. Eur. J. Pharmacol.56, 413–414 (1979).
Wachtel, H.: Inhibition of locomotor activity of rats by low doses of different dopamine (DA) receptor agonists. Naunyn-Schmiedeberg's Arch. Pharmacol.302, Suppl., R 59 (1978).
Westermann, K., Andreas, K.: Schablonentechnik bei elektrophysiologischen Fragestellungen und Perfusionsversuchen bei der Ratte. Acta Biol. Med. Germ.26, 1255–1258 (1971).
Woodruff, G. N., Andrews, C. D.: Some effects of sulpiride on dopaminergic systems: comparison with other neuroleptics. In: Sulpiride and Other Benzamides (Spano, P. F., Trabucchi, M., Corsini, G. U., Gessa, G. L., eds.), pp. 33–46. Milan: Italian Brain Research Foundation Press. 1979.
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Morgenstern, R., Fink, H. Sulpiride blocks postsynaptic dopamine receptors in the nucleus accumbens. J. Neural Transmission 61, 151–160 (1985). https://doi.org/10.1007/BF01251909
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DOI: https://doi.org/10.1007/BF01251909