Abstract
Development of tolerance to neuroleptic compounds tested in the conditional avoidance model was investigated. Since tolerance may manifest itself by a diminished potency and/or a shortened duration of effect, the complete time course of effect was registered in these experiments.
Rats were pretreated approximately 2 weeks with daily oral doses of chlorprothixene (20 mg/kg), flupenthixol (10 mg/kg), fluphenazine (2.5 mg/kg), or haloperidol (10 mg/kg) or twice a week with piflutixol (0.31 mg/kg). Three days after withdrawal chlorprothixene and flupenthixol caused a slightly but significantly weaker inhibition of avoidance performance in rats pretreated with the respective compounds and compared with non-pretreated rats, the duration of effect was shortened. Six days after withdrawal of piflutixol the duration of effect of a dose of piflutixol causing maximum inhibition was significantly shortened, while no homologous tolerance could be demonstrated in fluphenazine-pretreated rats. Cross tolerance was found after haloperidol-pretreatment when the rats were tested with fluphenazine 6 days after withdrawal. Homologous piflutixol tolerance could be shown 4 weeks after withdrawal.
These results indicate that it is possible to demonstrate a slight tolerance to the effect of neuroleptic compounds when these are tested in conditional avoidance experiments. The cause of this tolerance is discussed.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Allen, L. E., Ferguson, H. C., Cox, R. H., Jr.: Pharmacologic effects of MJ 9022-1, a potential tranquilizing agent. Arzneimittel-Forsch. 24, 917–922 (1974)
Asper, H., Baggiolini, M., Bürki, H. R., Lauener, H., Ruch, W., Stille, G.: Tolerance phenomena with neuroleptics. Catalepsy, apomorphine stereotypies and striatal dopamine metabolism in the rat after single and repeated administration of loxapine and haloperidol. Europ. J. Pharmacol. 22, 287–294 (1973)
Dominic, J. A., Moore, K. E.: Supersensitivity to the central stimulant actions of adrenergic drugs following discontinuation of a chronic diet of α-methyltyrosine. Psychopharmacologia (Berl.) 15, 96–101 (1969)
Fjalland, B., Møller Nielsen, I.: Enhancement of methylphenidate-induced stereotypies by repeated administration of neuroleptics. Psychopharmacologia (Berl.) 34, 105–109 (1974)
Hyttel, J.: Long-term effects of teflutixol on the synthesis and endogenous levels of mouse brain catecholamines. J. Neurochem. 25, 681–686 (1975)
Irwin, S.: Differential tolerance development to the avoidance and locomotor suppressant actions of perphenazine and chlorpromazine. Pharmacologist 3, 75 (1961)
Iwamoto, T., Matsuki, K.: Change of pharmacological effects by repeated administration of some tranquillizers. 53–56, 1st Symp. on Drug Metabolism and Action, November 14–15, 1969, in Chiba, Japan
Lang, W. J., Brown, M. L., Gershon, S., Sletten, I., Korol, B.: Effects of chronic chlorpromazine administration upon the blood pressure responses to autonomic drugs in conscious dogs. Arch. int. Pharmacodyn. 162, 330–344 (1966)
Møller Nielsen, I., Fjalland, B., Pedersen, V., Nymark, M.: Pharmacology of neuroleptics upon repeated administration. Psychopharmacologia (Berl.) 34, 95–104 (1974)
Møller Nielsen, I., Christensen, A. V.: Long term effects of neuroleptic drugs. J. Pharmacol. (Paris) 6, 277–282 (1975)
Schelkunov, E. L.: Adrenergic effect of chronic administration of neuroleptics. Nature (Lond.) 214, 1210–1212 (1967)
Stille, G., Lauener, H.: Die Wirkung von Neuroleptika im chronischen pharmakologischen Experiment. Arzneimittel-Forsch. 24, 1292–1294 (1974)
Theobald, W., Büch, O., Delini-Stula, A., Eigenmann R., Levin, Ph.: Pharmakologische Untersuchungen zur Wirkung von Neuroleptika am Tier nach einmaliger und wiederholter Applikation. Arzneimittel-Forsch. 18, 1491–1495 (1968)
Ungerstedt, U.: Postsynaptic supersensitivity after 6-hydroxy-dopamine induced degeneration of the nigro-striatal dopamine system. Acta physiol. scand, Suppl. 367, 69–93 (1971)
Waerden, B. L., van der, Nievergelt, E.: Tables for comparing two samples by X-test and sign test. Berlin-Göttingen-Heidelberg: Springer 1956
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Danneskiold-Samsøe, P., Pedersen, V. Inhibition of conditional avoidance response by neuroleptics upon repeated administration. Psychopharmacology 51, 9–14 (1976). https://doi.org/10.1007/BF00426314
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00426314