Abstract
Apomorphine induced dose-dependent hyperthermia when applied intravenously to rabbits pretreated with a monoamine oxidase inhibitor. Inhibition of the synthesis of catecholamines (by α-MT) did not influence on apomorphine-induced hyperthermia, whereas 5-HT synthesis inhibition (by PCPA) completely abolished the hyperthermic response. Some neuroleptics and a 5-HT receptor blocking agent inhibited the hyperthermia in very low doses. A highly significant correlation was registered between the antagonism of apomorphine hyperthermia of 15 neuroleptics and their clinically useful doses. It is concluded that apomorphine-induced hyperthermia most likely is a result of direct stimulation of dopamine receptors and release of 5-HT, and that abolition of this response represents a very sensitive in-vivo model for neuroleptic substances. Antagonism of apomorphine-induced hyperthermia may be achieved by either dopamine or 5-HT receptor blockade.
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References
Andén, N.-E., Rubinson, A., Fuxe, K., Hökfelt, T.: Evidence for dopamine receptor stimulation by apomorphine. J. Pharm. Pharmacol. 19, 627–629 (1967)
Burt, D. R., Creese, I., Snyder, S. H.: Properties of (3H) haloperidol and (3H) dopamine binding associated with dopamine receptors in calf brain membranes. Mol. Pharmacol. 12, 800–812 (1976)
Clineschmidt, B. V., Lotti, V. J.: Indolamine antagonists: relative potencies as inhibitors of tryptamine- and 5-hydroxytryptophanevoked responses. Br. J. Pharmacol. 50, 311–313 (1974)
Costall, B., Naylor, R. J.: A comparison of the abilities of typical neuroleptic agents and of thioridazine, clozapine, sulpiride and metoclopramide to antagonize the hyperactivity induced by dopamine applied intracerebrally to areas of the extrapyramidal and mesolimbic systems. Eur. J. Pharmacol. 40, 9–19 (1976)
Costall, B., Naylor, J.: Mesolimbic and extrapyramidal sites for the mediation of stereotyped behaviour patterns and hyperactivity by amphetamine and apomorphine in the rat. In: Cocaine and other stimulants, E. H. Ellinwood and M. M. Kilbey, eds. Adv. Behav. Biol. 21, 47–76 (1977)
Ernst, A. M.: Mode of action of apomorphine and dexamphetamine on gnawing compulsion in rats. Psychopharmacologia (Berl.) 10, 316–323 (1967)
Fjalland, B.: Neuroleptics influence on hyperthermia induced by 5-hydroxytryptophan and p-methoxy-amphetamine in MAOI-pretreated rabbits. Psychopharmacology 63, 113–117 (1979)
Hill, H. F., Horita, A.: A pimozide-sensitive effect of apomorphine on body temperature of the rabbit. J. Pharm. Pharmacol. 24, 490–491 (1972)
Janssen, R. A. J., Niemegeers, C. J. E., Schellekens, K. K. L.: Is it possible to predict the clinical effects of neuroleptic drugs from animal data? II. “Neuroleptic activity spectra” for dogs. Arzneim. Forsch. 15, 1196–1206 (1965)
Janssen, R. A. J., Lenaerts, F. M.: Is it possible to predict the clinical effects of neuroleptic drugs from animal data? IV. An improved experimental design for measuring the inhibitory effects of neuroleptic drugs on amphetamine- or apomorphine-induced “chewing” and “agitation” in rats. Arzneim. Forsch. 17, 841–854 (1967)
Leysen, J. E., Niemegeers, C. J. E., Tollenaere, J. P., Laduron, P. M.: Serotonergic component of neuroleptic receptors. Nature 272, 168–171 (1978)
Mawson, C., Whittington, H.: Evaluation of the peripheral and central antagonistic activities against 5-hydroxytryptamine of some new agents. Br. J. Pharmacol. 39, 223P (1970)
Miller, I., Freund, J. E.: Probability and statistics for engineers, pp. 254–258, New Jersey: Prentice-Hall 1965
Miller, R. J., Horn, A. S., Iversen, L. L.: The action of neuroleptic drugs on dopamine stimulated adenosine cyclic 3′,5′-monophosphate production in rat neostriatum and limbic forebrain. Mol. Pharmacol. 10, 759–766 (1975)
Nymark, M.: Apomorphine provoked stereotypy in the dog. Psychopharmacologia (Berl.) 26, 361–368 (1972)
Pycock, C. J., Tarsy, D., Marsden, C. D.: Inhibition of turning behaviour by clozapine in mice with unilateral destruction of dopaminergic nerve terminals. J. Pharm. Pharmacol. 27, 445–447 (1975)
Quock, R. M., Horita, A.: Apomorphine: Modification of its hyperthermic effect in rabbits by p-chlorophenylalanine. Science 183, 539–540 (1974)
Quock, R. M., Horita, A.: Differentiation of neuropharmacological actions of apomorphine and d-amphetamine. Pharmacol. Biochem. Behav. 5, 627–631 (1976)
Quock, R. M., Monserrat, A., Horita, A.: Thermotropic activity of apomorphine in the rabbit: a central site of a action. Life Sci. 16, 525–532 (1975)
Roszell, D. K., Horita, A.: The effects of haloperidol and thioridazine on apomorphine- and LSD-induced hyperthermia in the rabbit. J. Psychiatr. Res. 12, 117–123 (1975)
Stille, G., Lauener, H., Eichenberger, E.: The pharmacology of 8-chloro-11-(4-methyl-1-piperazinyl)-5H-dibenzo (b,e)(1,4) diazepine (clozapine). Farmaco. Edizione Practica 26, 603–625 (1971)
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Fjalland, B. Antagonism of apomorphine-induced hyperthermia in MAOI-pretreated rabbits as a sensitive model of neuroleptic activity. Psychopharmacology 63, 119–123 (1979). https://doi.org/10.1007/BF00429688
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DOI: https://doi.org/10.1007/BF00429688