Increase in rat striatal acetylcholine content by d-fenfluramine, a serotonin releaser

The anorectic agent, d-fenfluramine, maximally increased the acetylcholine content in the striatum by 50% at doses of 5-10 mg/kg. The action of the drug was completely prevented by treatments designed to interfere with serotonergic transmission (e.g., combined electrolytic lesion of the nucleus raphe medianus and dorsalis; pretreatments with methergoline, parachlorophenylalanine or fluoxetine). By contrast, interference with dopaminergic transmission (e.g., lesion of the nigrostriatal dopaminergic tract with 6-OHDA; pre-treatment with penfluridol) did not impede the action of d-fenfluramine. The administration of d-fenfluramine to animals given a supramaximal dose of apomorphine, 1.5 mg/kg, produced a summated increase in striatal acetylcholine. The data are consistent with the hypothesis that there may exist in the striatum different populations of cholinergic interneurons regulated by serotonin and dopamine, respectively.