Behavioral and Neurotransmitter Changes in the Urease-Infused Rat: A Model of Congenital Hyperammonemia

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Abstract
Rats implanted with subcutaneous or intraperitoneal osmotic minipumps infusing 0.8–1.25IU urease/ kg/h develop sustained hyperammonemia (range 137–497 µM, controls 88 ± 51 µM ± SD) for 5–7 days. Glutamine levels are also significantly elevated in plasma (677 ±166 versus 428 ± 122 µM) and cerebral cortex (13.2 ± 9.8 versus 4.7 ± 2.8 nmol/mg tissue). Neurobehavioral abnormalities include decreased food intake and increased stereotypic activity. Increased serotonin turnover was suggested by elevated levels of tryptophan and 5-hydroxyindoleacetic acid in cerebral cortex, brain stem, and cerebellum of urease-infused compared to sham-operated animals. There were no changes in norepinephrine or r aminobutyric acid, and there was no correlation between the degree of hyperammonemia or glutaminemia and brain levels of tryptophan or biogenic amines. Animals receiving a tryptophan- deficient diet had significantly lower levels of tryptophan and 5-hydroxyindoleacetic acid in brain regions compared to animals receiving a normal tryptophan intake, under both control and hyperammonemic conditions. Despite the prevention of increased serotonin flux in hyperammonemic animals receiving a tryptophan-deficient diet, food intake and weight declined and there was increased stereotypic behavior.