Abstract
In rabbits pretreated with i.p. probenecid, the hyperthermia induced by 5-hydroxytryptophan (5-HTP) was markedly potentiated. There was, however, no change in the level of 5-hydroxytryptamine (5-HT) in the hypothalamus and brain stem. Consequently, there is no direct relation in this situation between hyperthermia and the cerebral levels of 5-HT. High doses of Ro4-4602 inhibited the hyperthermic effect of 5-HTP and of 5-HTP in the presence of probenecid, although the levels of 5-HT in the hypothalamus and brain stem were elevated. At the same time, a decrease in the concentration of 5-hydroxyindolacetic acid (5-HIAA) was observed in the cerebrospinal fluid (CSF). The authors suggest from their findings that Ro4-4602 may inhibit the abnormal synthesis of 5-HT induced by an excess of 5-HTP in hypothalamic thermoregulatory structures other than 5-hydroxytryptaminergic structures.
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