Manipulations of synaptic serotonin: discrepancy of effects on serotonin S1 and S2 sites

The effect of repeated treatment (28 day) with D-fenfluramine, a serotonin (5HT) releaser, L-tryptophan, a 5HT precursor, or fluoxetine, a 5HT uptake inhibitor, on 3H-5HT and 3H-spiperone binding in the rat cerebral cortex was investigated. Treatment with fenfluramine and fluoxetine caused a significant decrease in the number of 3H-5HT binding sites (Bmax). Fenfluramine also decreased binding of 3H-spiperone in the cortex, but fluoxetine treatment increased this binding. Treatment with L-tryptophan produced no change in the binding of either 3H-5HT or of 3H-spiperone significantly. The data show that manipulation of synaptic 5HT concentration does not always result in parallel changes in S1 and S2 receptors. This suggests that the 5HT S1 and S2 receptors may be subject to different regulatory mechanisms.