Abstract
Hyperammonemia due to inherited deficiency of enzymes in the liver is also found in sparse-fur (spf) mice, which have OTC (ornithine transcarbamylase) deficiency, a high concentration of ammonia in the blood and a high concentration of glutamine and tryptophan after weaning. Abnormal behavior was observed during the hyperammonemic period in spf mice. Autonomic locomotor activity in spf mice during this period was enhanced under light but suppressed in the dark. The circadian rhythm of autonomic locomotor activity disappeared from 3 to 5 weeks and reappeared at 8 weeks. The frequency of the head twitch response induced by 5-methoxy-N, N-dimethyltryptamine (5-MeODMT) decreased in the hyperammonemic period, in which the concentration of brain tryptophan (Trp) and 5-hydroxyindoleacetic acid (5-HIAA) increased, the ratio of 5-HIAA to serotonin (5-HT) in the brain increased and [3H]-ketanserin binding to 5-HT2 receptor significantly decreased in the frontal cortex and whole brain. Down regulation in the postsynaptic 5-HT2 receptor may have provoked the inhibition of 5-MeODMT-induced head twitch response. The abnormal behavior of spf mice may derive from increased tryptophan in the brain due to hyperammonemia, increased 5-HT turnover rate and down regulation in the postsynaptic 5-HT2 receptor.
