Depletion of brain serotonin by chronic administration of p-chloroamphetamine orally to rats and dogs

Abstract

p-Chloroamphetamine (PCA) given in a single oral dose to rats lowered brain serotonin acutely almost as effectively as after ip injection. Likewise, PCA depleted brain serotonin when mixed with the diet, though the amount of food intake was reduced from that normally consumed due to the anorexic action of PCA. In one study in rats fed diets containing PCA for 125 days, the degree of brain serotonin and 5-hydroxyindoleacetic acid depletion was maximal at about 1–4 weeks and diminished during further drug ingestion by rats. In another study in rats fed diets containing PCA for 90 days, brain serotonin concentration was slightly but significantly reduced 2 weeks after drug administration was stopped. Brain serotonin concentration was decreased in dogs at the end of 90 days of oral drug administration and had not returned to control values 2 weeks after drug was discontinued. These results suggest that long-lasting (presumably neurotoxic) effects on brain serotonin neurons are less likely to occur when PCA is given orally than when it is injected ip.