Abstract
A marked tolerance to both analgesic and cataleptic effects of 20 mg/kg morphine hydrochloride was developed in rats during treatment with daily doses increasing from 20 to 120mg/kg s.c. within 11 days. Daily administration of 100 mg/kg sodium orotate i. p. 14 days before and during treatment with morphine significantly accelerated the development of tolerance for cataleptic as well as analgesic effects of morphine. The disappearance of the tolerance phenomena was delayed in the orotate-treated animals. No influence of orotate, however, could be observed on the formation of stereotyped behaviour and disappearance of stereotype.
The results support the assumption, that morphine tolerance may be an adaptive process in the CNS realized by RNA and protein syntheses in different neuronal cell populations. Treatment with the RNA precursor may improve this process, perhaps by enhancing RNA synthesis.
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This research was supported by the Ministerium für Wissenschaft und Technik der DDR.
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Grecksch, G., Ott, T. & Matthies, H. Effects of orotic acid on the development of morphine tolerance. Psychopharmacologia 36, 337–346 (1974). https://doi.org/10.1007/BF00422565
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DOI: https://doi.org/10.1007/BF00422565