Cognitive profile of rats exposed to lactational hyperphenylalaninemia: correspondence with human mental retardation.

The present study was designed to provide further information on the enduring cognitive effects of experimental phenylketonuria (PKU) in rats, produced by the administration of alpha-methylphenylalanine and phenylalanine on postnatal days 3-21. These rats evidenced: (1) impaired learning set formation, (2) stimulus perseveration, particularly after an error, and (3) difficulty in utilizing the less salient features of their environment in mastering discrimination problems. In contrast, long-term memory function and the ability to form simple associations did not differ from controls. This pattern of intact and impaired cognitive functions bears remarkable similarity to that of mentally retarded humans and neonatally hyperphenylalaninemic rhesus monkeys, thus affirming the use of rats to study mental retardation. In addition, possible reasons for the mildness of the impairments commonly observed in animal models of severe mental retardation syndromes are discussed. We suggest that transfer of learning paradigms that assess the animal's ability to use information acquired in other problems are more likely to uncover significant cognitive impairments in such models than are procedures that test only the animals' ability to solve a single problem.