SEROTONIN DEFICIENCY IN EXPERIMENTAL HYPERPHENYLALANINEMIA

Abstract— The mechanism of serotonin depletion was studied in the preweanling rat in which a chemical simulation of phenylketonuria had been induced by injections of p-CPA and l -PA. Experimental conditions were selected to effectively minimize the contribution by deficient tryptophan hydroxylation and 5-HTP transport. Excessive degradation of 5-HT in the hyperphenylalaninemic brain could be eliminated as a possible mechanism. The observed levels of cerebral 5-HTP, 5-HT, 5-HIAA before and 1 h after 5-HTP loading, with and without pargyline pretreatment, clearly demonstrate greatly diminished in vivo synthesis of 5-HT in the hyperphenylalaninemic animal. This deficient synthesis could largely be accounted for by decreased activity of aromatic l -amino acid decarboxylase measured in the high speed soluble supernatant extracts of whole brain. Decreased storage of 5-HT in the particulate subcellular fraction of whole brain was also noted in the hyperphenylalaninemic animal. Significant lowering of bound serotonin levels in the brain occurred with injections of PEA into normal animals.