Abstract
The development of tolerance, defined as a reduction in pharmacological potency, was studied in various experimental models following repeated administration of neuroleptic drugs to rats, mice and dogs.
Tolerance developed in all models involving stereotyped behaviour induced by central dopaminergic stimulation, whereas no tolerance developed to the cataleptogenic effect and the inhibition of conditioned avoidance reaction. Tolerance development was dependent on pretreatment dose and length of pretreatment period.
Once developed, tolerance persisted for a considerable time, particularly in rats and dogs. Several possible mechanisms by which tolerance could develop are discussed, among which the most likely appears to be 1. increased turnover of dopamine, leading to larger quanta of transmitter being released by the indirect sympathomimetic amine, or 2. increased receptor sensitivity following the prolonged receptor blockade.
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Nielsen, I.M., Fjalland, B., Pedersen, V. et al. Pharmacology of neuroleptics upon repeated administration. Psychopharmacologia 34, 95–104 (1974). https://doi.org/10.1007/BF00421933
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DOI: https://doi.org/10.1007/BF00421933