Effect of Phenylalanine Diet on Learning in the Rat

Phenylketonuria or Phenylpyruvic Oligophrenia in the Rat: Behavioural and Biochemical Correlates*

“…The second possibility is that the disease, as it occurs in humans, cannot be produced in the rat, and that retarded learning reported during the ingestion of the amino acid may have indicated only the acute, nonspecific toxicity of phenylalanine. This argument is supported by the data of Loo, et al, (1962) which showed that an avoidance response could not be conditioned in rats as long as they were fed a phenylalanine-supplemented diet which was started when the animals were weaned. However, after 45 days on a normal diet, the response was rapidly conditioned in the previously "retarded" animals.…”

“…That serum levels of phenylalanine were elevated and urinary excretion of phenylpyruvic acid was increased with dietary phenylalanine (Auerbach et al, 1958;Loo et al, 1962;Waisman ft al., 1959;Waisman, et al, 1960;Waisman and Harlow, 1965;Wang and Waisman, 1961) is evidence for the experimental production of phenylketonuria. However, there was no indication of phenylpyruvic oligophrenia because there was no evidence that the observed retardation was irreversible, i.e., learning was measured during the time of phenylalanine consumption rather than after a sul)stantial period of rtxovcry from the imnu-dialc effects of the amino acid.…”

Dietary Phenylalanine and Brain Function

“…Extensive laboratory and clinical studies have indicated the safety of aspartame, at least in normal populations (Aspinall et al 1980, Potts et al 1980, Ranney and Oppermann 1979, Stegink et al 1979 investigators have used phenylalanine to induce phenylketonuria, an inborn disorder of phenylalanine metabolism (Polidora et al 1966a,b, Waisman and Harlow 1965, Brunner et al 1979. Reports using this animal model of phenylketonuria have found deficits in learning associated with high dietary levels of phenylalanine (Loo et al 1962, Polidora et al 1963, 1966b. Schalock and Kloper (1967a,b) reported that when elevated levels of phenylalanine were introduced during prenatal or early postnatal development, long-lasting behavioral abnormalities could be observed.…”

Alteration in Composition of Deoxyribonucleic Acid, Ribonucleic Acid, Proteins, and Amino Acids in Brain of Rats Fed High and Low Phenylalanine Diets

“…The high levels of phenylalanine found in blood and brain of phenylketonuric children (PKU) appear to produce severe brain damage, since a diet low in phenylalanine instituted during the first weeks of life permits nearly normal development [5]. Brain development is also affected in rats fed excessive quantities of L-phcnylalanine [15,26]. Recent reports [4,8,12] indicated that excessive depletion of phenylalanine retards growth and mental development of children and impairs the ability of rats to perform in behavior tests.…”