Abstract
The time course of different pharmacological effects of l-5-hydroxytryptophan (5-HTP) during continued treatment was studied in rats. 5-HTP was administered three times daily at 100 mg/kg IP in combination with the peripheral decarboxylase inhibitor carbidopa (10 mg/kg) for 14 days. 5-HTP induced a pronounced increase of the threshold for maximal electroconvulsions, decreased body temperature and body weight and induced characteristic “wet-dog” shake behaviour. Whereas the anticonvulsant effect increased during the 14 days of treatment, tolerance developed to the excitatory and, less rapidly, to the hypothermic and anorexigenic effects of 5-HTP. Biochemical determinations showed marked increases in 5-HTP and its metabolites, 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid, in both plasma and brain throughout the period of treatment. The mechanisms underlying the different time-courses of the functional effects of 5-HTP during continued treatment are not clear, but effects on catecholaminergic systems as well as regional differences in 5-HT increases in the brain might be involved.
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Pagliusi, S.R., Löscher, W. Development of tolerance to the wet-dog shake behaviour but not the increase in seizure threshold induced by l-5-hydroxytryptophan during continued treatment in rats. Psychopharmacology 86, 118–124 (1985). https://doi.org/10.1007/BF00431695
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DOI: https://doi.org/10.1007/BF00431695