Repeated treatment with d-fenfluramine or metergoline alters cortex binding of 3H-serotonin and serotenergic sensitivity in rats.

28-day treatment with d-fenfluramine, a serotonin (5HT) releaser and uptake inhibitor, caused significant reduction (23%) of 3H-5HT binding sites (Bmax) in the rat cortex. These sites were significantly increased (31%) in cortical membranes of rats which had received metergoline, a potent serotonin antagonist, for 28 days. Parallel changes were found in the anorectic activity of metachlorophenylpiperazine (m-CPP), a potent central 5HT agonist: chronic treatment with d-fenfluramine or metergoline caused respectively a decrease and in the effect of m-CPP on food intake. The data show that changes in 5HT central receptor number and sensitivity may occur after chronic treatment with drugs acting on brain serotonin.