Hyper- and hyposensitivity of central serotonin receptors: [3H]serotonin binding and functional studies in the rat

The effect of repeated treatment with d-fenfluramine, a serotonin releaser, or methergoline, a serotonin antagonist, on [³H]5-HT binding was studied in various rat brain areas. In animals with the same pretreatments, the anorectic activity of m-chlorophenylpiperazine, a serotonin agonist, was investigated. A 14-day treatment with d-fenfluramine caused a significant decrease in the number of [³H]5-HT binding sites (B_max) in the diencephalon. A reduction of binding sites was found in the cortex too when d-fenfluramine was administered for 28 days. Methergoline caused no changes of [³H]5-HT binding in any brain area exmined when given for 14 days but 28-day treatment led to a significant increase in the striatum, hippocampus and cortex. d-Fenfluramine and methergoline caused, respectively, a decrease and increase in the effect of m-chlorophenylpiperazine on food intake. The data show that central 5-HT receptor numbers and sensitivity may change after repeated treatments with drugs acting on brain serotonin.