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.
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.
Pagliusi
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SR
Löscher
W
W
D006916:5-Hydroxytryptophan / Q000032:analysis / Q000494:pharmacology*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D002230:Carbidopa / Q000494:pharmacology; D004347:Drug Interactions; D004361:Drug Tolerance; D005260:Female; D006897:Hydroxyindoleacetic Acid / Q000032:analysis; D009069:Movement Disorders / Q000139:chemically induced*; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced*; D012701:Serotonin / Q000032:analysis
D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D006916:5-Hydroxytryptophan; D002230:Carbidopa