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The enduring behavioral changes in rats with experimental phenylketonuria.

The biochemical features of phenylketonuria have been reproduced in developing rat pups by administering to them a combination of p-chloro-DL-phenylalanine plus L-phenylalanine for the first 21 days after birth. During the treatment period, the experimental animals show delayed eye opening and decreased brain weight compared with controls given saline. Neuropathological examination of developing animals reveals deficient myelination and some inhibition of cerebellar maturation. When tested as adults, after a long recovery period, animals with phenylketonuria are hyperactive in activity wheels. Adult rats are deficient in reversing a position choice and demonstrate impaired performance in a Y-maze. Rats treated with p-chloro-DL-phenylalanine plus L-phenylalanine during the vulnerable period of rapid brain development thus have enduring behavioral changes that persist throughout life.